Pulmonary Perspectives®

The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.

As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.

CHEST

Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).

A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).

Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.

CHEST

It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.

The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.



Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.

The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.

As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.

CHEST

Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).

A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).

Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.

CHEST

It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.

The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.



Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.

The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.

As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.

CHEST

Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).

A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).

Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.

CHEST

It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.

The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.



Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.

The SARS-CoV-2 pandemic changed the way intensivists approach extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 acute respiratory distress syndrome (ARDS) placed on ECMO have a high prevalence of right ventricular (RV) failure, which is associated with reduced survival (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). In 2021, our institution supported 51 patients with COVID-19 ARDS with ECMO: 51% developed RV failure, defined as a clinical syndrome (reduced cardiac output) in the presence of RV dysfunction on transthoracic echocardiogram (TTE) (Marra A et al. Chest. 2022;161[2]:535). Total numbers for RV dysfunction and RV dilation on TTE were 78% and 91% respectively, so many of those with RV changes on TTE did not progress to clinical failure. In essence then, TTE signs of RV dysfunction are sensitive but not specific for clinical RV failure.

Rates for survival to decannulation were far lower when RV failure was present (27%) vs. absent (84%). Given these numbers, we felt a reduction in RV failure would be an important target for improving outcomes for patients with COVID-19 ARDS receiving ECMO. Existing studies on RV failure in patients with ARDS receiving ECMO are plagued by scant data, small sample sizes, differences in diagnostic criteria, and heterogenous treatment approaches. Despite these limitations, we felt the need to make changes in our approach to RV management.

Because outcomes once clinical RV-failure occurs are so poor, we focused on prevention. While we’re short on data and evidence-based medicine (EBM) here, we know a lot about the physiology of COVID19, the pulmonary vasculature, and the right side of the heart. There are multiple physiologic and disease-related pathways that converge to produce RV-failure in patients with COVID-19 ARDS on ECMO (Sato R et al. Crit Care. 2021;25:172). Ongoing relative hypoxemia, hypercapnia, acidemia, and microvascular thromboses/immunothromboses can all lead to increased pulmonary vascular resistance (PVR) and an increased workload for the RV (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). ARDS management typically involves high positive end-expiratory pressure (PEEP), which can produce RV-PA uncoupling (Wanner P et al. J Clin Med. 2020;9:432).

We do know that ECMO relieves the stress on the right side of the heart by improving hypoxemia, hypercapnia, and acidemia while allowing for reduction in PEEP (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). In addition to ECMO, proning and pulmonary vasodilators offload RV by further reducing pulmonary pressures (Sato R et al. Crit Care. 2021;25:172). Lastly, a right ventricular assist device (RVAD) can dissipate the work required by the RV and prevent decompensation. Collectively, these therapies can be considered preventive.

Knowing the RV parameters on RV are sensitive but not specific for outcomes though, when should some of these treatments be instituted? It’s clear that once RV failure has developed it’s probably too late, but it’s hard to find data to guide us on when to act. One institution used right ventricular assist devices (RVADs) at the time of ECMO initiation with protocolized care and achieved a survival to discharge rate of 73% (Mustafa AK et al. JAMA Surgery. 2020;155[10]:990). The publication generated enthusiasm for RVAD support with ECMO, but it’s possible the protocolized care drove the high survival rate, at least in part.

At our institution, we developed our own protocol for evaluation of the RV with proactive treatment based on specific targets. We performed daily, bedside TTE and assessed the RV fractional area of change (FAC) and outflow tract velocity time integral (VTI). These parameters provide a quantitative assessment of global RV function, and FAC is directly related to ability to wean from ECMO support (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). We avoided using the tricuspid annular plain systolic excursion (TAPSE) due to its poor sensitivity (Marra AM et al. Chest. 2022;161[2]:535). Patients receiving ECMO with subjective, global mild to moderate RV dysfunction on TTE with worsening clinical data, an FAC of 20%-35%, and a VTI of 10-14 cm were treated with aggressive diuresis, pulmonary vasodilators, and inotropy for 48 hours. If there was no improvement or deterioration, an RVAD was placed. For patients with signs of severe RV dysfunction (FAC < 20% or VTI < 10 cm), we proceeded directly to RVAD. We’re currently collecting data and tracking outcomes.

While data exist on various interventions in RV failure due to COVID-19 ARDS with ECMO, our understanding of this disease is still in its infancy. The optimal timing of interventions to manage and prevent RV failure is not known. We would argue that those who wait for RV failure to occur before instituting protective or supportive therapies are missing the opportunity to impact outcomes. We currently do not have the evidence to support the specific protocol we’ve outlined here and instituted at our hospital. However, we do believe there’s enough literature and experience to support the concept that close monitoring of RV function is critical for patients with COVID19 ARDS receiving ECMO. Failure to anticipate worsening function on the way to failure means reacting to it rather than staving it off. By then, it’s too late.
 

Dr. Thomas is Maj, USAF, assistant professor, pulmonary/critical care; Dr. O’Neil is Maj, USAF, pediatric and ECMO intensivist, PICU medical director; and Dr. Villalobos is Capt, USAF, assistant professor, pulmonary/critical care, medical ICU director, Brooke Army Medical Center, San Antonio, Tex. The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, or the Department of Defense or the U.S. government.

The SARS-CoV-2 pandemic changed the way intensivists approach extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 acute respiratory distress syndrome (ARDS) placed on ECMO have a high prevalence of right ventricular (RV) failure, which is associated with reduced survival (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). In 2021, our institution supported 51 patients with COVID-19 ARDS with ECMO: 51% developed RV failure, defined as a clinical syndrome (reduced cardiac output) in the presence of RV dysfunction on transthoracic echocardiogram (TTE) (Marra A et al. Chest. 2022;161[2]:535). Total numbers for RV dysfunction and RV dilation on TTE were 78% and 91% respectively, so many of those with RV changes on TTE did not progress to clinical failure. In essence then, TTE signs of RV dysfunction are sensitive but not specific for clinical RV failure.

Rates for survival to decannulation were far lower when RV failure was present (27%) vs. absent (84%). Given these numbers, we felt a reduction in RV failure would be an important target for improving outcomes for patients with COVID-19 ARDS receiving ECMO. Existing studies on RV failure in patients with ARDS receiving ECMO are plagued by scant data, small sample sizes, differences in diagnostic criteria, and heterogenous treatment approaches. Despite these limitations, we felt the need to make changes in our approach to RV management.

Because outcomes once clinical RV-failure occurs are so poor, we focused on prevention. While we’re short on data and evidence-based medicine (EBM) here, we know a lot about the physiology of COVID19, the pulmonary vasculature, and the right side of the heart. There are multiple physiologic and disease-related pathways that converge to produce RV-failure in patients with COVID-19 ARDS on ECMO (Sato R et al. Crit Care. 2021;25:172). Ongoing relative hypoxemia, hypercapnia, acidemia, and microvascular thromboses/immunothromboses can all lead to increased pulmonary vascular resistance (PVR) and an increased workload for the RV (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). ARDS management typically involves high positive end-expiratory pressure (PEEP), which can produce RV-PA uncoupling (Wanner P et al. J Clin Med. 2020;9:432).

We do know that ECMO relieves the stress on the right side of the heart by improving hypoxemia, hypercapnia, and acidemia while allowing for reduction in PEEP (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). In addition to ECMO, proning and pulmonary vasodilators offload RV by further reducing pulmonary pressures (Sato R et al. Crit Care. 2021;25:172). Lastly, a right ventricular assist device (RVAD) can dissipate the work required by the RV and prevent decompensation. Collectively, these therapies can be considered preventive.

Knowing the RV parameters on RV are sensitive but not specific for outcomes though, when should some of these treatments be instituted? It’s clear that once RV failure has developed it’s probably too late, but it’s hard to find data to guide us on when to act. One institution used right ventricular assist devices (RVADs) at the time of ECMO initiation with protocolized care and achieved a survival to discharge rate of 73% (Mustafa AK et al. JAMA Surgery. 2020;155[10]:990). The publication generated enthusiasm for RVAD support with ECMO, but it’s possible the protocolized care drove the high survival rate, at least in part.

At our institution, we developed our own protocol for evaluation of the RV with proactive treatment based on specific targets. We performed daily, bedside TTE and assessed the RV fractional area of change (FAC) and outflow tract velocity time integral (VTI). These parameters provide a quantitative assessment of global RV function, and FAC is directly related to ability to wean from ECMO support (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). We avoided using the tricuspid annular plain systolic excursion (TAPSE) due to its poor sensitivity (Marra AM et al. Chest. 2022;161[2]:535). Patients receiving ECMO with subjective, global mild to moderate RV dysfunction on TTE with worsening clinical data, an FAC of 20%-35%, and a VTI of 10-14 cm were treated with aggressive diuresis, pulmonary vasodilators, and inotropy for 48 hours. If there was no improvement or deterioration, an RVAD was placed. For patients with signs of severe RV dysfunction (FAC < 20% or VTI < 10 cm), we proceeded directly to RVAD. We’re currently collecting data and tracking outcomes.

While data exist on various interventions in RV failure due to COVID-19 ARDS with ECMO, our understanding of this disease is still in its infancy. The optimal timing of interventions to manage and prevent RV failure is not known. We would argue that those who wait for RV failure to occur before instituting protective or supportive therapies are missing the opportunity to impact outcomes. We currently do not have the evidence to support the specific protocol we’ve outlined here and instituted at our hospital. However, we do believe there’s enough literature and experience to support the concept that close monitoring of RV function is critical for patients with COVID19 ARDS receiving ECMO. Failure to anticipate worsening function on the way to failure means reacting to it rather than staving it off. By then, it’s too late.
 

Dr. Thomas is Maj, USAF, assistant professor, pulmonary/critical care; Dr. O’Neil is Maj, USAF, pediatric and ECMO intensivist, PICU medical director; and Dr. Villalobos is Capt, USAF, assistant professor, pulmonary/critical care, medical ICU director, Brooke Army Medical Center, San Antonio, Tex. The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, or the Department of Defense or the U.S. government.

The SARS-CoV-2 pandemic changed the way intensivists approach extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 acute respiratory distress syndrome (ARDS) placed on ECMO have a high prevalence of right ventricular (RV) failure, which is associated with reduced survival (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). In 2021, our institution supported 51 patients with COVID-19 ARDS with ECMO: 51% developed RV failure, defined as a clinical syndrome (reduced cardiac output) in the presence of RV dysfunction on transthoracic echocardiogram (TTE) (Marra A et al. Chest. 2022;161[2]:535). Total numbers for RV dysfunction and RV dilation on TTE were 78% and 91% respectively, so many of those with RV changes on TTE did not progress to clinical failure. In essence then, TTE signs of RV dysfunction are sensitive but not specific for clinical RV failure.

Rates for survival to decannulation were far lower when RV failure was present (27%) vs. absent (84%). Given these numbers, we felt a reduction in RV failure would be an important target for improving outcomes for patients with COVID-19 ARDS receiving ECMO. Existing studies on RV failure in patients with ARDS receiving ECMO are plagued by scant data, small sample sizes, differences in diagnostic criteria, and heterogenous treatment approaches. Despite these limitations, we felt the need to make changes in our approach to RV management.

Because outcomes once clinical RV-failure occurs are so poor, we focused on prevention. While we’re short on data and evidence-based medicine (EBM) here, we know a lot about the physiology of COVID19, the pulmonary vasculature, and the right side of the heart. There are multiple physiologic and disease-related pathways that converge to produce RV-failure in patients with COVID-19 ARDS on ECMO (Sato R et al. Crit Care. 2021;25:172). Ongoing relative hypoxemia, hypercapnia, acidemia, and microvascular thromboses/immunothromboses can all lead to increased pulmonary vascular resistance (PVR) and an increased workload for the RV (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). ARDS management typically involves high positive end-expiratory pressure (PEEP), which can produce RV-PA uncoupling (Wanner P et al. J Clin Med. 2020;9:432).

We do know that ECMO relieves the stress on the right side of the heart by improving hypoxemia, hypercapnia, and acidemia while allowing for reduction in PEEP (Zochios V et al. ASAIO Journal. 2022; 68[4]:456). In addition to ECMO, proning and pulmonary vasodilators offload RV by further reducing pulmonary pressures (Sato R et al. Crit Care. 2021;25:172). Lastly, a right ventricular assist device (RVAD) can dissipate the work required by the RV and prevent decompensation. Collectively, these therapies can be considered preventive.

Knowing the RV parameters on RV are sensitive but not specific for outcomes though, when should some of these treatments be instituted? It’s clear that once RV failure has developed it’s probably too late, but it’s hard to find data to guide us on when to act. One institution used right ventricular assist devices (RVADs) at the time of ECMO initiation with protocolized care and achieved a survival to discharge rate of 73% (Mustafa AK et al. JAMA Surgery. 2020;155[10]:990). The publication generated enthusiasm for RVAD support with ECMO, but it’s possible the protocolized care drove the high survival rate, at least in part.

At our institution, we developed our own protocol for evaluation of the RV with proactive treatment based on specific targets. We performed daily, bedside TTE and assessed the RV fractional area of change (FAC) and outflow tract velocity time integral (VTI). These parameters provide a quantitative assessment of global RV function, and FAC is directly related to ability to wean from ECMO support (Maharaj V et al. ASAIO Journal. 2022;68[6]:772). We avoided using the tricuspid annular plain systolic excursion (TAPSE) due to its poor sensitivity (Marra AM et al. Chest. 2022;161[2]:535). Patients receiving ECMO with subjective, global mild to moderate RV dysfunction on TTE with worsening clinical data, an FAC of 20%-35%, and a VTI of 10-14 cm were treated with aggressive diuresis, pulmonary vasodilators, and inotropy for 48 hours. If there was no improvement or deterioration, an RVAD was placed. For patients with signs of severe RV dysfunction (FAC < 20% or VTI < 10 cm), we proceeded directly to RVAD. We’re currently collecting data and tracking outcomes.

While data exist on various interventions in RV failure due to COVID-19 ARDS with ECMO, our understanding of this disease is still in its infancy. The optimal timing of interventions to manage and prevent RV failure is not known. We would argue that those who wait for RV failure to occur before instituting protective or supportive therapies are missing the opportunity to impact outcomes. We currently do not have the evidence to support the specific protocol we’ve outlined here and instituted at our hospital. However, we do believe there’s enough literature and experience to support the concept that close monitoring of RV function is critical for patients with COVID19 ARDS receiving ECMO. Failure to anticipate worsening function on the way to failure means reacting to it rather than staving it off. By then, it’s too late.
 

Dr. Thomas is Maj, USAF, assistant professor, pulmonary/critical care; Dr. O’Neil is Maj, USAF, pediatric and ECMO intensivist, PICU medical director; and Dr. Villalobos is Capt, USAF, assistant professor, pulmonary/critical care, medical ICU director, Brooke Army Medical Center, San Antonio, Tex. The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, or the Department of Defense or the U.S. government.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

Point-of-care ultrasound (POCUS) is a useful, practice-changing bedside tool that spans all medical and surgical specialties. While the definition of POCUS varies, most would agree it is an abbreviated exam that helps to answer a specific clinical question. With the expansion of POCUS training, the clinical questions being asked and answered have increased in scope and volume. The types of exams being utilized in “point of care ultrasound” have also increased and include transthoracic echocardiography; trans-esophageal echocardiography; and lung, gastric, abdominal, and ocular ultrasound. POCUS is used across multiple specialties, including critical care, anesthesiology, emergency medicine, and primary care.

CHEST

Not only has POCUS become increasingly important clinically, but specialties now test these skills on their respective board examinations. Anesthesia is one of many such examples. The content outline for the American Board of Anesthesiology includes POCUS as a tested item on both the written and applied components of the exam. POCUS training must be directed toward both optimizing patient management and preparing learners for their board examination. A method for teaching this has yet to be defined (Naji A, et al. Cureus. 2021;13[5]:e15217).

One question – how should different specialties approach this educational challenge and should specialties train together? The answer is complicated. Many POCUS courses and certifications exist, and all vary in their content, didactics, and length. No true gold standard exists for POCUS certification for radiology or noncardiology providers. Additionally, there are no defined expectations or testing processes that certify a provider is “certified” to perform POCUS. While waiting for medical society guidelines to address these issues, many in graduate medical education (GME) are coming up with their own ways to incorporate POCUS into their respective training programs (Atkinson P, et al. CJEM. 2015 Mar;17[2]:161).

Who’s training whom?

Over the past decade, several expert committees, including those in critical care, have developed recommendations and consensus statements urging training facilities to independently create POCUS curriculums. The threshold for many programs to enter this realm of expertise is high and oftentimes unobtainable. We’ve seen emergency medicine and anesthesia raise the bar for ultrasound education in their residencies, but it’s unclear whether all fellowship-trained physicians can and should be tasked with obtaining official POCUS certification.

While specific specialties may require tailored certifications, there’s a considerable overlap in POCUS exam content across specialties. One approach to POCUS training could be developing and implementing a multidisciplinary curriculum. This would allow for pooling of resources (equipment, staff) and harnessing knowledge from providers familiar with different phases of patient care (ICU, perioperative, ED, outpatient clinics). By approaching POCUS from a multidisciplinary perspective, the quality of education may be enhanced (Mayo PH, et al. Intensive Care Med. 2014;40[5]:654). Is it then prudent for providers and trainees alike to share in didactics across all areas of the hospital and clinic? Would this close the knowledge gap between specialties who are facile with ultrasound and those not?

Determining the role of transesophageal echocardiography in a POCUS curriculum

This modality of imaging has been, until recently, reserved for cardiologists and anesthesiologists. More recently transesophageal echocardiography (TEE) has been utilized by emergency and critical care medicine physicians. TEE is part of recommended training for these specialties as a tool for diagnostic and rescue measures, including ventilator management, emergency procedures, and medication titration. Rescue TEE can also be utilized perioperatively where the transthoracic exam is limited by poor windows or the operative procedure precludes access to the chest. While transthoracic echocardiography (TTE) is often used in a point of care fashion, TEE is utilized less often. This may stem from the invasive nature of the procedure but likely also results from lack of equipment and training. Like POCUS overall, TEE POCUS will require incorporation into training programs to achieve widespread use and acceptance.

A deluge of research on TEE for the noncardiologist shows this modality is minimally invasive, safe, and effective. As it becomes more readily available and technology improves, there is no reason why an esophageal probe can’t be used in a patient with a secured airway (Wray TC, et al. J Intensive Care Med. 2021;36[1]:123).

Ultrasound for hemodynamic monitoring

There are many methods employed for hemodynamic monitoring in the ICU. Although echocardiographic and vascular parameters have been validated in the cardiac and perioperative fields, their application in the ICU setting for resuscitation and volume management remain somewhat controversial. The use of TEE and more advanced understanding of spectral doppler and pulmonary ultrasonography using TEE has revolutionized the way providers are managing critically ill patients. (Garcia YA, et al. Chest. 2017;152[4]:736).

In our opinion, physiology and imaging training for residents and fellows should be required for critical care medicine trainees. Delving into the nuances of frank-starling curves, stroke work, and diastolic function will enrich their understanding and highlight the applicability of ultrasonography. Furthermore, all clinicians caring for patients with critical illness should be privy to the nuances of physiologic derangement, and to that end, advanced echocardiographic principles and image acquisition. The heart-lung interactions are demonstrated in real time using POCUS and can clearly delineate treatment goals (Vieillard-Baron A, et al. Intensive Care Med. 2019;45[6]:770).

Documentation and billing

If clinicians are making medical decisions based off imaging gathered at the bedside and interpreted in real-time, documentation should reflect that. That documentation will invariably lead to billing and possibly audit or quality review by colleagues or other healthcare staff. Radiology and cardiology have perfected the billing process for image interpretation, but their form of documentation and interpretation may not easily be implemented in the perioperative or critical care settings. An abbreviated document with focused information should take the place of the formal study. With that, the credentialing and board certification process will allow providers to feel empowered to make clinical decisions based off these focused examinations.

Dr. Goertzen is Chief Fellow, Pulmonary/Critical Care; Dr. Knuf is Program Director, Department of Anesthesia; and Dr. Villalobos is Director of Medical ICU, Department of Internal Medicine, San Antonio Military Medical Center, San Antonio, Texas.

Point-of-care ultrasound (POCUS) is a useful, practice-changing bedside tool that spans all medical and surgical specialties. While the definition of POCUS varies, most would agree it is an abbreviated exam that helps to answer a specific clinical question. With the expansion of POCUS training, the clinical questions being asked and answered have increased in scope and volume. The types of exams being utilized in “point of care ultrasound” have also increased and include transthoracic echocardiography; trans-esophageal echocardiography; and lung, gastric, abdominal, and ocular ultrasound. POCUS is used across multiple specialties, including critical care, anesthesiology, emergency medicine, and primary care.

CHEST

Not only has POCUS become increasingly important clinically, but specialties now test these skills on their respective board examinations. Anesthesia is one of many such examples. The content outline for the American Board of Anesthesiology includes POCUS as a tested item on both the written and applied components of the exam. POCUS training must be directed toward both optimizing patient management and preparing learners for their board examination. A method for teaching this has yet to be defined (Naji A, et al. Cureus. 2021;13[5]:e15217).

One question – how should different specialties approach this educational challenge and should specialties train together? The answer is complicated. Many POCUS courses and certifications exist, and all vary in their content, didactics, and length. No true gold standard exists for POCUS certification for radiology or noncardiology providers. Additionally, there are no defined expectations or testing processes that certify a provider is “certified” to perform POCUS. While waiting for medical society guidelines to address these issues, many in graduate medical education (GME) are coming up with their own ways to incorporate POCUS into their respective training programs (Atkinson P, et al. CJEM. 2015 Mar;17[2]:161).

Who’s training whom?

Over the past decade, several expert committees, including those in critical care, have developed recommendations and consensus statements urging training facilities to independently create POCUS curriculums. The threshold for many programs to enter this realm of expertise is high and oftentimes unobtainable. We’ve seen emergency medicine and anesthesia raise the bar for ultrasound education in their residencies, but it’s unclear whether all fellowship-trained physicians can and should be tasked with obtaining official POCUS certification.

While specific specialties may require tailored certifications, there’s a considerable overlap in POCUS exam content across specialties. One approach to POCUS training could be developing and implementing a multidisciplinary curriculum. This would allow for pooling of resources (equipment, staff) and harnessing knowledge from providers familiar with different phases of patient care (ICU, perioperative, ED, outpatient clinics). By approaching POCUS from a multidisciplinary perspective, the quality of education may be enhanced (Mayo PH, et al. Intensive Care Med. 2014;40[5]:654). Is it then prudent for providers and trainees alike to share in didactics across all areas of the hospital and clinic? Would this close the knowledge gap between specialties who are facile with ultrasound and those not?

Determining the role of transesophageal echocardiography in a POCUS curriculum

This modality of imaging has been, until recently, reserved for cardiologists and anesthesiologists. More recently transesophageal echocardiography (TEE) has been utilized by emergency and critical care medicine physicians. TEE is part of recommended training for these specialties as a tool for diagnostic and rescue measures, including ventilator management, emergency procedures, and medication titration. Rescue TEE can also be utilized perioperatively where the transthoracic exam is limited by poor windows or the operative procedure precludes access to the chest. While transthoracic echocardiography (TTE) is often used in a point of care fashion, TEE is utilized less often. This may stem from the invasive nature of the procedure but likely also results from lack of equipment and training. Like POCUS overall, TEE POCUS will require incorporation into training programs to achieve widespread use and acceptance.

A deluge of research on TEE for the noncardiologist shows this modality is minimally invasive, safe, and effective. As it becomes more readily available and technology improves, there is no reason why an esophageal probe can’t be used in a patient with a secured airway (Wray TC, et al. J Intensive Care Med. 2021;36[1]:123).

Ultrasound for hemodynamic monitoring

There are many methods employed for hemodynamic monitoring in the ICU. Although echocardiographic and vascular parameters have been validated in the cardiac and perioperative fields, their application in the ICU setting for resuscitation and volume management remain somewhat controversial. The use of TEE and more advanced understanding of spectral doppler and pulmonary ultrasonography using TEE has revolutionized the way providers are managing critically ill patients. (Garcia YA, et al. Chest. 2017;152[4]:736).

In our opinion, physiology and imaging training for residents and fellows should be required for critical care medicine trainees. Delving into the nuances of frank-starling curves, stroke work, and diastolic function will enrich their understanding and highlight the applicability of ultrasonography. Furthermore, all clinicians caring for patients with critical illness should be privy to the nuances of physiologic derangement, and to that end, advanced echocardiographic principles and image acquisition. The heart-lung interactions are demonstrated in real time using POCUS and can clearly delineate treatment goals (Vieillard-Baron A, et al. Intensive Care Med. 2019;45[6]:770).

Documentation and billing

If clinicians are making medical decisions based off imaging gathered at the bedside and interpreted in real-time, documentation should reflect that. That documentation will invariably lead to billing and possibly audit or quality review by colleagues or other healthcare staff. Radiology and cardiology have perfected the billing process for image interpretation, but their form of documentation and interpretation may not easily be implemented in the perioperative or critical care settings. An abbreviated document with focused information should take the place of the formal study. With that, the credentialing and board certification process will allow providers to feel empowered to make clinical decisions based off these focused examinations.

Dr. Goertzen is Chief Fellow, Pulmonary/Critical Care; Dr. Knuf is Program Director, Department of Anesthesia; and Dr. Villalobos is Director of Medical ICU, Department of Internal Medicine, San Antonio Military Medical Center, San Antonio, Texas.

Point-of-care ultrasound (POCUS) is a useful, practice-changing bedside tool that spans all medical and surgical specialties. While the definition of POCUS varies, most would agree it is an abbreviated exam that helps to answer a specific clinical question. With the expansion of POCUS training, the clinical questions being asked and answered have increased in scope and volume. The types of exams being utilized in “point of care ultrasound” have also increased and include transthoracic echocardiography; trans-esophageal echocardiography; and lung, gastric, abdominal, and ocular ultrasound. POCUS is used across multiple specialties, including critical care, anesthesiology, emergency medicine, and primary care.

CHEST

Not only has POCUS become increasingly important clinically, but specialties now test these skills on their respective board examinations. Anesthesia is one of many such examples. The content outline for the American Board of Anesthesiology includes POCUS as a tested item on both the written and applied components of the exam. POCUS training must be directed toward both optimizing patient management and preparing learners for their board examination. A method for teaching this has yet to be defined (Naji A, et al. Cureus. 2021;13[5]:e15217).

One question – how should different specialties approach this educational challenge and should specialties train together? The answer is complicated. Many POCUS courses and certifications exist, and all vary in their content, didactics, and length. No true gold standard exists for POCUS certification for radiology or noncardiology providers. Additionally, there are no defined expectations or testing processes that certify a provider is “certified” to perform POCUS. While waiting for medical society guidelines to address these issues, many in graduate medical education (GME) are coming up with their own ways to incorporate POCUS into their respective training programs (Atkinson P, et al. CJEM. 2015 Mar;17[2]:161).

Who’s training whom?

Over the past decade, several expert committees, including those in critical care, have developed recommendations and consensus statements urging training facilities to independently create POCUS curriculums. The threshold for many programs to enter this realm of expertise is high and oftentimes unobtainable. We’ve seen emergency medicine and anesthesia raise the bar for ultrasound education in their residencies, but it’s unclear whether all fellowship-trained physicians can and should be tasked with obtaining official POCUS certification.

While specific specialties may require tailored certifications, there’s a considerable overlap in POCUS exam content across specialties. One approach to POCUS training could be developing and implementing a multidisciplinary curriculum. This would allow for pooling of resources (equipment, staff) and harnessing knowledge from providers familiar with different phases of patient care (ICU, perioperative, ED, outpatient clinics). By approaching POCUS from a multidisciplinary perspective, the quality of education may be enhanced (Mayo PH, et al. Intensive Care Med. 2014;40[5]:654). Is it then prudent for providers and trainees alike to share in didactics across all areas of the hospital and clinic? Would this close the knowledge gap between specialties who are facile with ultrasound and those not?

Determining the role of transesophageal echocardiography in a POCUS curriculum

This modality of imaging has been, until recently, reserved for cardiologists and anesthesiologists. More recently transesophageal echocardiography (TEE) has been utilized by emergency and critical care medicine physicians. TEE is part of recommended training for these specialties as a tool for diagnostic and rescue measures, including ventilator management, emergency procedures, and medication titration. Rescue TEE can also be utilized perioperatively where the transthoracic exam is limited by poor windows or the operative procedure precludes access to the chest. While transthoracic echocardiography (TTE) is often used in a point of care fashion, TEE is utilized less often. This may stem from the invasive nature of the procedure but likely also results from lack of equipment and training. Like POCUS overall, TEE POCUS will require incorporation into training programs to achieve widespread use and acceptance.

A deluge of research on TEE for the noncardiologist shows this modality is minimally invasive, safe, and effective. As it becomes more readily available and technology improves, there is no reason why an esophageal probe can’t be used in a patient with a secured airway (Wray TC, et al. J Intensive Care Med. 2021;36[1]:123).

Ultrasound for hemodynamic monitoring

There are many methods employed for hemodynamic monitoring in the ICU. Although echocardiographic and vascular parameters have been validated in the cardiac and perioperative fields, their application in the ICU setting for resuscitation and volume management remain somewhat controversial. The use of TEE and more advanced understanding of spectral doppler and pulmonary ultrasonography using TEE has revolutionized the way providers are managing critically ill patients. (Garcia YA, et al. Chest. 2017;152[4]:736).

In our opinion, physiology and imaging training for residents and fellows should be required for critical care medicine trainees. Delving into the nuances of frank-starling curves, stroke work, and diastolic function will enrich their understanding and highlight the applicability of ultrasonography. Furthermore, all clinicians caring for patients with critical illness should be privy to the nuances of physiologic derangement, and to that end, advanced echocardiographic principles and image acquisition. The heart-lung interactions are demonstrated in real time using POCUS and can clearly delineate treatment goals (Vieillard-Baron A, et al. Intensive Care Med. 2019;45[6]:770).

Documentation and billing

If clinicians are making medical decisions based off imaging gathered at the bedside and interpreted in real-time, documentation should reflect that. That documentation will invariably lead to billing and possibly audit or quality review by colleagues or other healthcare staff. Radiology and cardiology have perfected the billing process for image interpretation, but their form of documentation and interpretation may not easily be implemented in the perioperative or critical care settings. An abbreviated document with focused information should take the place of the formal study. With that, the credentialing and board certification process will allow providers to feel empowered to make clinical decisions based off these focused examinations.

Dr. Goertzen is Chief Fellow, Pulmonary/Critical Care; Dr. Knuf is Program Director, Department of Anesthesia; and Dr. Villalobos is Director of Medical ICU, Department of Internal Medicine, San Antonio Military Medical Center, San Antonio, Texas.

Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.

In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).

Courtesy ACCP

However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).

Courtesy ACCP

More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV₁). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).

What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.

But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?

A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).

Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).

Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.

So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.

Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.

Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.

Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.

In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).

Courtesy ACCP

However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).

Courtesy ACCP

More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV₁). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).

What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.

But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?

A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).

Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).

Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.

So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.

Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.

Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.

Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.

In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).

Courtesy ACCP

However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).

Courtesy ACCP

More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV₁). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).

What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.

But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?

A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).

Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).

Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.

So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.

Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.

Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.

The SARS-CoV-2 pandemic required health care systems around the world to rapidly innovate and adapt to unprecedented operational and clinical strain. Many health care systems leveraged virtual care capabilities as an innovative approach to safely and efficiently manage patients while reducing staff exposure and medical resource constraints (Healthcare [Basel]. 2020 Nov;8[4]:517; JMIR Form Res. 2021 Jan; 5[1]:e23190). With Medicare insurance claims data demonstrating a 30% reduction of in-person health visits, telemedicine has become an essential means to fill the gaps in providing essential medical services (JAMA Intern Med. 2021 Mar;181[3]:388-91). A vast majority of virtual health care visits come via telephonic encounters, which have inherent limitations in the ability to monitor patients with complex or critical medical conditions (Front Public Health. 2020;8:410; N Engl J Med. 2020 Apr;382[18]:1679-81). Remote patient monitoring (RPM) has been established in multiple clinical models as an effective adjunct in telemedicine encounters in order to ensure treatment regimen adherence, make real-time treatment adjustments, and identify patients at risk for early decompensation.

Long-term RPM data has demonstrated cost reduction, reduced burden of in-office visits, expedited management of significant clinical events, and decreased all-cause mortality rates. Previously RPM was limited to the care of patients with chronic conditions, particularly cardiac patients with congestive heart failure and invasive devices, such as pacemakers or implantable cardioverter–defibrillators (JMIR Form Res. 2021 Jan;5[1]:e23190; Front Public Health. 2020; 8:410). In response to the pandemic, the Centers for Medicare and Medicaid Services (CMS) added RPM billing codes in 2019 and then included coverage of acute conditions in 2020 that permitted a more extensive role of RPM in telemedicine. This change in financial reimbursement led to a more aggressive expansion of RPM devices to assess physiologic parameters, such as weight, blood pressure, oxygen saturation, and blood glucose levels for clinicians to review.

Courtesy ACCP

Currently, RPM devices fall within a low-risk FDA category that do not require clinical trials for validation prior to being cleared for CMS billing in a fee-for-service reimbursement model (N Engl J Med. 2021 Apr;384[15]:1384-6). A shortage of evidence-based publications to guide clinicians in this new landscape creates challenges from underuse, misuse, or abuse of RPM tools. In order to maximize the clinical benefits of RPM, standardized processes and device specifications derived from up-to-date research need to be established in professional society guidelines.

Courtesy ACCP

Formalized RPM protocols should play a key role in overcoming the hesitancy of health institutions becoming early adopters of RPM technologies. Some significant challenges leading to reluctance of executing an RPM program were recently highlighted at the REPROGRAM international consortium of telemedicine. These concerns involved building a technological infrastructure, training clinical staff, ensuring remote connectivity with broadband Internet, and working with patients of various technologic literacy (Front Public Health. 2020;8:410). We attempted to address these challenges by using a COVID-19 remote patient monitoring (CRPM) strategy within our Military Health System (MHS). By using the well-established responsible, accountable, consulted, and informed (RACI) matrix process mapping tool, we created a standardized enrollment process of high-risk patients across eight military treatment facilities (MTFs). High risk patients included those with COVID-19 pneumonia and persistent hypoxemia, those recovering from acute exacerbations of congestive heart failure, those with cardiopulmonary instability associated with malignancy, and other conditions that required continuous monitoring outside of the hospital setting.

Courtesy ACCP

In our CRPM process, the hospital inpatient unit or ED refer high-risk patients to a primary designated provider at each MTF for enrollment prior to discharge. Enrolled patients are equipped with an FDA-approved home monitoring kit that contains an electronic tablet, a network hub that operates independently of and/or in conjunction with Wi-Fi, and an armband containing a coin-sized monitor. The system has the capability to pair with additional smart-enabled accessories, such as a blood pressure cuff, temperature patch, and digital spirometer. With continuous bio-physiologic and symptom-based monitoring, a team of teleworking critical-care nurses monitor patients continuously. In case of a decompensation necessitating a higher level of care, an emergency action plan (EAP) is activated to ensure patients urgently receive emergency medical services. Once released from the CRPM program, discharged patients use prepaid shipping boxes to facilitate contactless repackaging, sanitization, and pickup for redistribution of devices to the MTF.

Courtesy ACCP

Given the increased number of hospital admissions noted during the COVID-19 global pandemic, the CRPM program has allowed us to address overutilization of hospital beds. Furthermore, it has allowed us to address issues of screening and resource utilization as we consider patients for safe implementation of home monitoring. While data concerning the outcome of the CRPM program are pending, we are encouraged about the ability to provide high quality care in a remote setting. To that end, we have addressed technologic difficulties, communication between remote providers and patients in the home environment, and communication between health care providers in various settings, such as the ED, inpatient wards, and the outpatient clinic.

Courtesy ACCP

To be sure, there are many challenges in making sure that CRPM adequately addresses the needs of patients, who may have persistent perturbations in cardiopulmonary status, tremendous anxiety about the progress or deterioration in their health status, and lack of understanding about their medical condition. Furthermore, providers face the challenge of making clinical decisions sometimes without the advantage of in-person examinations. Sometimes decisions must be made with incomplete information or when the status of the patient does not follow presupposed algorithms. Nevertheless, like many issues during the COVID-19 pandemic, patients and providers have evolved, pivoted, and made necessary adjustments to address an unprecedented time in recent history.

Ultimately, we believe that a continuous remote patient monitoring program can be designed, implemented, and maintained across a multifacility health care system for safe, effective, and efficient health care delivery. Limitations in implementing such a program might include lack of adequate Internet services, lack of telephonic communication, inadequate home facilities, lack of adequate home support, and, perhaps, lack of available emergency services. However, if the conditions for home monitoring are optimized, CRPM holds the promise of reducing the burden on emergency and inpatient hospital services, particularly when those services are strained in circumstances such as the ongoing global pandemic due to COVID-19. With further study, standardization, and evolution, remote monitoring will likely become a more acceptable and necessary form of health care delivery in the future.
 

Dr. Salomon is an Internal Medicine Resident (PGY-2); Dr. Muller is an Internal Medicine Resident (PGY-2); Dr. Boster is a Pulmonary and Critical Care Fellow; Dr. Loudermilk is a Pulmonary and Critical Care Fellow; and Dr. Kemp is Pulmonary and Critical Care staff, San Antonio Military Medical Center, Fort Sam Houston, Texas.

The SARS-CoV-2 pandemic required health care systems around the world to rapidly innovate and adapt to unprecedented operational and clinical strain. Many health care systems leveraged virtual care capabilities as an innovative approach to safely and efficiently manage patients while reducing staff exposure and medical resource constraints (Healthcare [Basel]. 2020 Nov;8[4]:517; JMIR Form Res. 2021 Jan; 5[1]:e23190). With Medicare insurance claims data demonstrating a 30% reduction of in-person health visits, telemedicine has become an essential means to fill the gaps in providing essential medical services (JAMA Intern Med. 2021 Mar;181[3]:388-91). A vast majority of virtual health care visits come via telephonic encounters, which have inherent limitations in the ability to monitor patients with complex or critical medical conditions (Front Public Health. 2020;8:410; N Engl J Med. 2020 Apr;382[18]:1679-81). Remote patient monitoring (RPM) has been established in multiple clinical models as an effective adjunct in telemedicine encounters in order to ensure treatment regimen adherence, make real-time treatment adjustments, and identify patients at risk for early decompensation.

Long-term RPM data has demonstrated cost reduction, reduced burden of in-office visits, expedited management of significant clinical events, and decreased all-cause mortality rates. Previously RPM was limited to the care of patients with chronic conditions, particularly cardiac patients with congestive heart failure and invasive devices, such as pacemakers or implantable cardioverter–defibrillators (JMIR Form Res. 2021 Jan;5[1]:e23190; Front Public Health. 2020; 8:410). In response to the pandemic, the Centers for Medicare and Medicaid Services (CMS) added RPM billing codes in 2019 and then included coverage of acute conditions in 2020 that permitted a more extensive role of RPM in telemedicine. This change in financial reimbursement led to a more aggressive expansion of RPM devices to assess physiologic parameters, such as weight, blood pressure, oxygen saturation, and blood glucose levels for clinicians to review.

Courtesy ACCP

Currently, RPM devices fall within a low-risk FDA category that do not require clinical trials for validation prior to being cleared for CMS billing in a fee-for-service reimbursement model (N Engl J Med. 2021 Apr;384[15]:1384-6). A shortage of evidence-based publications to guide clinicians in this new landscape creates challenges from underuse, misuse, or abuse of RPM tools. In order to maximize the clinical benefits of RPM, standardized processes and device specifications derived from up-to-date research need to be established in professional society guidelines.

Courtesy ACCP

Formalized RPM protocols should play a key role in overcoming the hesitancy of health institutions becoming early adopters of RPM technologies. Some significant challenges leading to reluctance of executing an RPM program were recently highlighted at the REPROGRAM international consortium of telemedicine. These concerns involved building a technological infrastructure, training clinical staff, ensuring remote connectivity with broadband Internet, and working with patients of various technologic literacy (Front Public Health. 2020;8:410). We attempted to address these challenges by using a COVID-19 remote patient monitoring (CRPM) strategy within our Military Health System (MHS). By using the well-established responsible, accountable, consulted, and informed (RACI) matrix process mapping tool, we created a standardized enrollment process of high-risk patients across eight military treatment facilities (MTFs). High risk patients included those with COVID-19 pneumonia and persistent hypoxemia, those recovering from acute exacerbations of congestive heart failure, those with cardiopulmonary instability associated with malignancy, and other conditions that required continuous monitoring outside of the hospital setting.

Courtesy ACCP

In our CRPM process, the hospital inpatient unit or ED refer high-risk patients to a primary designated provider at each MTF for enrollment prior to discharge. Enrolled patients are equipped with an FDA-approved home monitoring kit that contains an electronic tablet, a network hub that operates independently of and/or in conjunction with Wi-Fi, and an armband containing a coin-sized monitor. The system has the capability to pair with additional smart-enabled accessories, such as a blood pressure cuff, temperature patch, and digital spirometer. With continuous bio-physiologic and symptom-based monitoring, a team of teleworking critical-care nurses monitor patients continuously. In case of a decompensation necessitating a higher level of care, an emergency action plan (EAP) is activated to ensure patients urgently receive emergency medical services. Once released from the CRPM program, discharged patients use prepaid shipping boxes to facilitate contactless repackaging, sanitization, and pickup for redistribution of devices to the MTF.

Courtesy ACCP

Given the increased number of hospital admissions noted during the COVID-19 global pandemic, the CRPM program has allowed us to address overutilization of hospital beds. Furthermore, it has allowed us to address issues of screening and resource utilization as we consider patients for safe implementation of home monitoring. While data concerning the outcome of the CRPM program are pending, we are encouraged about the ability to provide high quality care in a remote setting. To that end, we have addressed technologic difficulties, communication between remote providers and patients in the home environment, and communication between health care providers in various settings, such as the ED, inpatient wards, and the outpatient clinic.

Courtesy ACCP

To be sure, there are many challenges in making sure that CRPM adequately addresses the needs of patients, who may have persistent perturbations in cardiopulmonary status, tremendous anxiety about the progress or deterioration in their health status, and lack of understanding about their medical condition. Furthermore, providers face the challenge of making clinical decisions sometimes without the advantage of in-person examinations. Sometimes decisions must be made with incomplete information or when the status of the patient does not follow presupposed algorithms. Nevertheless, like many issues during the COVID-19 pandemic, patients and providers have evolved, pivoted, and made necessary adjustments to address an unprecedented time in recent history.

Ultimately, we believe that a continuous remote patient monitoring program can be designed, implemented, and maintained across a multifacility health care system for safe, effective, and efficient health care delivery. Limitations in implementing such a program might include lack of adequate Internet services, lack of telephonic communication, inadequate home facilities, lack of adequate home support, and, perhaps, lack of available emergency services. However, if the conditions for home monitoring are optimized, CRPM holds the promise of reducing the burden on emergency and inpatient hospital services, particularly when those services are strained in circumstances such as the ongoing global pandemic due to COVID-19. With further study, standardization, and evolution, remote monitoring will likely become a more acceptable and necessary form of health care delivery in the future.
 

Dr. Salomon is an Internal Medicine Resident (PGY-2); Dr. Muller is an Internal Medicine Resident (PGY-2); Dr. Boster is a Pulmonary and Critical Care Fellow; Dr. Loudermilk is a Pulmonary and Critical Care Fellow; and Dr. Kemp is Pulmonary and Critical Care staff, San Antonio Military Medical Center, Fort Sam Houston, Texas.

The SARS-CoV-2 pandemic required health care systems around the world to rapidly innovate and adapt to unprecedented operational and clinical strain. Many health care systems leveraged virtual care capabilities as an innovative approach to safely and efficiently manage patients while reducing staff exposure and medical resource constraints (Healthcare [Basel]. 2020 Nov;8[4]:517; JMIR Form Res. 2021 Jan; 5[1]:e23190). With Medicare insurance claims data demonstrating a 30% reduction of in-person health visits, telemedicine has become an essential means to fill the gaps in providing essential medical services (JAMA Intern Med. 2021 Mar;181[3]:388-91). A vast majority of virtual health care visits come via telephonic encounters, which have inherent limitations in the ability to monitor patients with complex or critical medical conditions (Front Public Health. 2020;8:410; N Engl J Med. 2020 Apr;382[18]:1679-81). Remote patient monitoring (RPM) has been established in multiple clinical models as an effective adjunct in telemedicine encounters in order to ensure treatment regimen adherence, make real-time treatment adjustments, and identify patients at risk for early decompensation.

Long-term RPM data has demonstrated cost reduction, reduced burden of in-office visits, expedited management of significant clinical events, and decreased all-cause mortality rates. Previously RPM was limited to the care of patients with chronic conditions, particularly cardiac patients with congestive heart failure and invasive devices, such as pacemakers or implantable cardioverter–defibrillators (JMIR Form Res. 2021 Jan;5[1]:e23190; Front Public Health. 2020; 8:410). In response to the pandemic, the Centers for Medicare and Medicaid Services (CMS) added RPM billing codes in 2019 and then included coverage of acute conditions in 2020 that permitted a more extensive role of RPM in telemedicine. This change in financial reimbursement led to a more aggressive expansion of RPM devices to assess physiologic parameters, such as weight, blood pressure, oxygen saturation, and blood glucose levels for clinicians to review.

Courtesy ACCP

Currently, RPM devices fall within a low-risk FDA category that do not require clinical trials for validation prior to being cleared for CMS billing in a fee-for-service reimbursement model (N Engl J Med. 2021 Apr;384[15]:1384-6). A shortage of evidence-based publications to guide clinicians in this new landscape creates challenges from underuse, misuse, or abuse of RPM tools. In order to maximize the clinical benefits of RPM, standardized processes and device specifications derived from up-to-date research need to be established in professional society guidelines.

Courtesy ACCP

Formalized RPM protocols should play a key role in overcoming the hesitancy of health institutions becoming early adopters of RPM technologies. Some significant challenges leading to reluctance of executing an RPM program were recently highlighted at the REPROGRAM international consortium of telemedicine. These concerns involved building a technological infrastructure, training clinical staff, ensuring remote connectivity with broadband Internet, and working with patients of various technologic literacy (Front Public Health. 2020;8:410). We attempted to address these challenges by using a COVID-19 remote patient monitoring (CRPM) strategy within our Military Health System (MHS). By using the well-established responsible, accountable, consulted, and informed (RACI) matrix process mapping tool, we created a standardized enrollment process of high-risk patients across eight military treatment facilities (MTFs). High risk patients included those with COVID-19 pneumonia and persistent hypoxemia, those recovering from acute exacerbations of congestive heart failure, those with cardiopulmonary instability associated with malignancy, and other conditions that required continuous monitoring outside of the hospital setting.

Courtesy ACCP

In our CRPM process, the hospital inpatient unit or ED refer high-risk patients to a primary designated provider at each MTF for enrollment prior to discharge. Enrolled patients are equipped with an FDA-approved home monitoring kit that contains an electronic tablet, a network hub that operates independently of and/or in conjunction with Wi-Fi, and an armband containing a coin-sized monitor. The system has the capability to pair with additional smart-enabled accessories, such as a blood pressure cuff, temperature patch, and digital spirometer. With continuous bio-physiologic and symptom-based monitoring, a team of teleworking critical-care nurses monitor patients continuously. In case of a decompensation necessitating a higher level of care, an emergency action plan (EAP) is activated to ensure patients urgently receive emergency medical services. Once released from the CRPM program, discharged patients use prepaid shipping boxes to facilitate contactless repackaging, sanitization, and pickup for redistribution of devices to the MTF.

Courtesy ACCP

Given the increased number of hospital admissions noted during the COVID-19 global pandemic, the CRPM program has allowed us to address overutilization of hospital beds. Furthermore, it has allowed us to address issues of screening and resource utilization as we consider patients for safe implementation of home monitoring. While data concerning the outcome of the CRPM program are pending, we are encouraged about the ability to provide high quality care in a remote setting. To that end, we have addressed technologic difficulties, communication between remote providers and patients in the home environment, and communication between health care providers in various settings, such as the ED, inpatient wards, and the outpatient clinic.

Courtesy ACCP

To be sure, there are many challenges in making sure that CRPM adequately addresses the needs of patients, who may have persistent perturbations in cardiopulmonary status, tremendous anxiety about the progress or deterioration in their health status, and lack of understanding about their medical condition. Furthermore, providers face the challenge of making clinical decisions sometimes without the advantage of in-person examinations. Sometimes decisions must be made with incomplete information or when the status of the patient does not follow presupposed algorithms. Nevertheless, like many issues during the COVID-19 pandemic, patients and providers have evolved, pivoted, and made necessary adjustments to address an unprecedented time in recent history.

Ultimately, we believe that a continuous remote patient monitoring program can be designed, implemented, and maintained across a multifacility health care system for safe, effective, and efficient health care delivery. Limitations in implementing such a program might include lack of adequate Internet services, lack of telephonic communication, inadequate home facilities, lack of adequate home support, and, perhaps, lack of available emergency services. However, if the conditions for home monitoring are optimized, CRPM holds the promise of reducing the burden on emergency and inpatient hospital services, particularly when those services are strained in circumstances such as the ongoing global pandemic due to COVID-19. With further study, standardization, and evolution, remote monitoring will likely become a more acceptable and necessary form of health care delivery in the future.
 

Dr. Salomon is an Internal Medicine Resident (PGY-2); Dr. Muller is an Internal Medicine Resident (PGY-2); Dr. Boster is a Pulmonary and Critical Care Fellow; Dr. Loudermilk is a Pulmonary and Critical Care Fellow; and Dr. Kemp is Pulmonary and Critical Care staff, San Antonio Military Medical Center, Fort Sam Houston, Texas.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

It’s day 1 of “attendingship,” and I’m back to wearing my white coat after years of being confident enough in myself to think I didn’t need it to look like “the doctor.” Is it okay to park here? Does my clinic have a staff bathroom? Will my log in work? Oh my gosh, how do I place orders?! I remember this feeling – it’s intern year all over again, except there’s no senior resident to rescue me now – here we go!

Starting off

As a new attending, the amount of responsibility can be intimidating and overwhelming. It is important to remember that you are not alone, you have a whole team supporting you whether you are in clinic or the ICU. Be sure to introduce yourself to those who you will be working with, get to know them, their roles, and figure out the best way that you can help each other with the ultimate goal of helping patients. In addition to meeting your own team, it is important to introduce yourself to your new colleagues – especially if you are new to the institution. Drs. Fielder and Sihag suggest putting together an introductory email to those who may be referring to you that includes an overview of what you do and how you can help, as well as your contact information. They also suggest maintaining an open line of communication and keeping the referring provider updated on your mutual patient (Fiedler AG, Sihag S. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1156-60). While this may sound antiquated, in my experience thus far, my colleagues have greatly appreciated this gesture.

Finding support

Even though you will be surrounded by a plethora of new colleagues, the transition to attending can be lonely – especially if you are moving to a new institution. Be sure to keep in touch with your co-residents, co-fellows, mentors, and, of course, your friends and family. Studies have shown that support mitigates stress and reduces job strain, which can lead to better health outcomes in the long term (Fiedler AG, Sihag S. [above]). Another great source of support for me is my CHEST colleagues. If you have not already, I highly suggest joining the CHEST Network(s) that aligns with your career interests. This is a great way to not only network with those who share the same niche as you but also to explore academic opportunities outside of your institution. Through the CHEST Home Mechanical Ventilation and Sleep NetWorks, I have gained mentors, made friends, and have become more involved in CHEST’s annual meeting, chairing my first session this year.

Staying organized

Adjusting to your new schedule can be just as hard as adjusting to a new role or new institution. After years of moving through the well-oiled, regimented machine that is medical training, there are suddenly no more rotations, no more research blocks, and no more protected time for learning. Dr. Okereke suggests creating a weekly calendar, which blocks time for not only your clinical duties but for studying (as you will be taking boards during your first year), academic endeavors (teaching and/or research), and, most importantly – for fun (Okereke I. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1161-2). Being cognizant about maintaining work-life balance is key once you become an attending. It is finally time to learn how to take time off, away from all things work, and to not feel guilty about it.

Saying no

This brings me to saying “no.” We are taught to say “yes” to every opportunity throughout our careers and, while that can certainly help us get far, it can also lead to burnout. Once you’re an attending, you’re in it for the long haul, so best to say yes to the things you are most interested in and “spark joy,” as Marie Kondo says, and say no to the things that do not make you happy and are not congruent with your overall goals. Fielder and Sihag (above) note that your division director or chief typically has a vision in mind for you within the department. It is important to communicate with leadership so that everyone is on the same page and the administrative and academic opportunities afforded to you are in alignment with your career goals going forward.

Teaching trainees

To prepare for teaching as an attending, Dr. Greco recommends starting during your own training. She suggests cataloging your study materials and notes for later reference, curating talks throughout your training, and exploring different rounding styles prior to graduation (Greco, A. CHEST Thought Leader Blog. 2021 June). To get more experience in formal speaking, Dr. Shen and colleagues encourage getting involved in resident noon conferences (Shen JZ, Memon AA, Lin C. Stroke. 2019 Sep;50[9]:e250-e252). A benefit of being a critical care attending is that you can gain experience teaching not only with the internal medicine residents but with emergency medicine, anesthesiology, and critical care advanced practice provider residents, as well.

While lecturing is one thing, teaching on service is a whole different ball game. No matter how young, fun, and relatable you think you are, you’re the boss now. You’re the giver of grades and the writer of evaluations. It is important to be self-aware of your influence and be deliberate with the environment you create on rounds and in clinic. Set expectations on day 1 so that everyone understands. Be open with what you are working on. For example, I make daily goals for myself that I share with the team before rounds. Drs. Fielder and Sihag (above) suggest sharing anecdotes from your own time in training that can help both you and your trainees remember that you were just in their shoes. Allowing yourself to be vulnerable creates a safe space in which your learners feel more comfortable doing the same.

Lastly, delegation is key. While many of us have done this since residency, Dr. Shen et al (above) suggest deliberately practicing this during fellowship. If you were the fellow who was able to handle a lot on your own, trust that your own fellows will be able to do that. Delegating to your trainees helps you improve personal and team efficiency, provides fellows with needed autonomy, and allows you to further grow into the role of attending physician.
 

Conclusion

While you may be nervous starting out, trust that you have been well trained and have the clinical knowledge and skills you need to do your job – you are ready. Get to know the staff you will be working with, your colleagues, and keep in touch with your co-trainees and mentors who have helped you along the way. Make daily goals for yourself, and make time to read and reflect so that you can continue to learn and grow. Most of all, make time for yourself, your friends, and your family, because after years of supporting you through all of your hard work, you’ve finally made it – congrats!

Dr. Greer is Assistant Professor of Medicine, Emory University Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Atlanta, GA.

It’s day 1 of “attendingship,” and I’m back to wearing my white coat after years of being confident enough in myself to think I didn’t need it to look like “the doctor.” Is it okay to park here? Does my clinic have a staff bathroom? Will my log in work? Oh my gosh, how do I place orders?! I remember this feeling – it’s intern year all over again, except there’s no senior resident to rescue me now – here we go!

Starting off

As a new attending, the amount of responsibility can be intimidating and overwhelming. It is important to remember that you are not alone, you have a whole team supporting you whether you are in clinic or the ICU. Be sure to introduce yourself to those who you will be working with, get to know them, their roles, and figure out the best way that you can help each other with the ultimate goal of helping patients. In addition to meeting your own team, it is important to introduce yourself to your new colleagues – especially if you are new to the institution. Drs. Fielder and Sihag suggest putting together an introductory email to those who may be referring to you that includes an overview of what you do and how you can help, as well as your contact information. They also suggest maintaining an open line of communication and keeping the referring provider updated on your mutual patient (Fiedler AG, Sihag S. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1156-60). While this may sound antiquated, in my experience thus far, my colleagues have greatly appreciated this gesture.

Finding support

Even though you will be surrounded by a plethora of new colleagues, the transition to attending can be lonely – especially if you are moving to a new institution. Be sure to keep in touch with your co-residents, co-fellows, mentors, and, of course, your friends and family. Studies have shown that support mitigates stress and reduces job strain, which can lead to better health outcomes in the long term (Fiedler AG, Sihag S. [above]). Another great source of support for me is my CHEST colleagues. If you have not already, I highly suggest joining the CHEST Network(s) that aligns with your career interests. This is a great way to not only network with those who share the same niche as you but also to explore academic opportunities outside of your institution. Through the CHEST Home Mechanical Ventilation and Sleep NetWorks, I have gained mentors, made friends, and have become more involved in CHEST’s annual meeting, chairing my first session this year.

Staying organized

Adjusting to your new schedule can be just as hard as adjusting to a new role or new institution. After years of moving through the well-oiled, regimented machine that is medical training, there are suddenly no more rotations, no more research blocks, and no more protected time for learning. Dr. Okereke suggests creating a weekly calendar, which blocks time for not only your clinical duties but for studying (as you will be taking boards during your first year), academic endeavors (teaching and/or research), and, most importantly – for fun (Okereke I. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1161-2). Being cognizant about maintaining work-life balance is key once you become an attending. It is finally time to learn how to take time off, away from all things work, and to not feel guilty about it.

Saying no

This brings me to saying “no.” We are taught to say “yes” to every opportunity throughout our careers and, while that can certainly help us get far, it can also lead to burnout. Once you’re an attending, you’re in it for the long haul, so best to say yes to the things you are most interested in and “spark joy,” as Marie Kondo says, and say no to the things that do not make you happy and are not congruent with your overall goals. Fielder and Sihag (above) note that your division director or chief typically has a vision in mind for you within the department. It is important to communicate with leadership so that everyone is on the same page and the administrative and academic opportunities afforded to you are in alignment with your career goals going forward.

Teaching trainees

To prepare for teaching as an attending, Dr. Greco recommends starting during your own training. She suggests cataloging your study materials and notes for later reference, curating talks throughout your training, and exploring different rounding styles prior to graduation (Greco, A. CHEST Thought Leader Blog. 2021 June). To get more experience in formal speaking, Dr. Shen and colleagues encourage getting involved in resident noon conferences (Shen JZ, Memon AA, Lin C. Stroke. 2019 Sep;50[9]:e250-e252). A benefit of being a critical care attending is that you can gain experience teaching not only with the internal medicine residents but with emergency medicine, anesthesiology, and critical care advanced practice provider residents, as well.

While lecturing is one thing, teaching on service is a whole different ball game. No matter how young, fun, and relatable you think you are, you’re the boss now. You’re the giver of grades and the writer of evaluations. It is important to be self-aware of your influence and be deliberate with the environment you create on rounds and in clinic. Set expectations on day 1 so that everyone understands. Be open with what you are working on. For example, I make daily goals for myself that I share with the team before rounds. Drs. Fielder and Sihag (above) suggest sharing anecdotes from your own time in training that can help both you and your trainees remember that you were just in their shoes. Allowing yourself to be vulnerable creates a safe space in which your learners feel more comfortable doing the same.

Lastly, delegation is key. While many of us have done this since residency, Dr. Shen et al (above) suggest deliberately practicing this during fellowship. If you were the fellow who was able to handle a lot on your own, trust that your own fellows will be able to do that. Delegating to your trainees helps you improve personal and team efficiency, provides fellows with needed autonomy, and allows you to further grow into the role of attending physician.
 

Conclusion

While you may be nervous starting out, trust that you have been well trained and have the clinical knowledge and skills you need to do your job – you are ready. Get to know the staff you will be working with, your colleagues, and keep in touch with your co-trainees and mentors who have helped you along the way. Make daily goals for yourself, and make time to read and reflect so that you can continue to learn and grow. Most of all, make time for yourself, your friends, and your family, because after years of supporting you through all of your hard work, you’ve finally made it – congrats!

Dr. Greer is Assistant Professor of Medicine, Emory University Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Atlanta, GA.

It’s day 1 of “attendingship,” and I’m back to wearing my white coat after years of being confident enough in myself to think I didn’t need it to look like “the doctor.” Is it okay to park here? Does my clinic have a staff bathroom? Will my log in work? Oh my gosh, how do I place orders?! I remember this feeling – it’s intern year all over again, except there’s no senior resident to rescue me now – here we go!

Starting off

As a new attending, the amount of responsibility can be intimidating and overwhelming. It is important to remember that you are not alone, you have a whole team supporting you whether you are in clinic or the ICU. Be sure to introduce yourself to those who you will be working with, get to know them, their roles, and figure out the best way that you can help each other with the ultimate goal of helping patients. In addition to meeting your own team, it is important to introduce yourself to your new colleagues – especially if you are new to the institution. Drs. Fielder and Sihag suggest putting together an introductory email to those who may be referring to you that includes an overview of what you do and how you can help, as well as your contact information. They also suggest maintaining an open line of communication and keeping the referring provider updated on your mutual patient (Fiedler AG, Sihag S. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1156-60). While this may sound antiquated, in my experience thus far, my colleagues have greatly appreciated this gesture.

Finding support

Even though you will be surrounded by a plethora of new colleagues, the transition to attending can be lonely – especially if you are moving to a new institution. Be sure to keep in touch with your co-residents, co-fellows, mentors, and, of course, your friends and family. Studies have shown that support mitigates stress and reduces job strain, which can lead to better health outcomes in the long term (Fiedler AG, Sihag S. [above]). Another great source of support for me is my CHEST colleagues. If you have not already, I highly suggest joining the CHEST Network(s) that aligns with your career interests. This is a great way to not only network with those who share the same niche as you but also to explore academic opportunities outside of your institution. Through the CHEST Home Mechanical Ventilation and Sleep NetWorks, I have gained mentors, made friends, and have become more involved in CHEST’s annual meeting, chairing my first session this year.

Staying organized

Adjusting to your new schedule can be just as hard as adjusting to a new role or new institution. After years of moving through the well-oiled, regimented machine that is medical training, there are suddenly no more rotations, no more research blocks, and no more protected time for learning. Dr. Okereke suggests creating a weekly calendar, which blocks time for not only your clinical duties but for studying (as you will be taking boards during your first year), academic endeavors (teaching and/or research), and, most importantly – for fun (Okereke I. J Thorac Cardiovasc Surg. 2020 Mar;159[3]:1161-2). Being cognizant about maintaining work-life balance is key once you become an attending. It is finally time to learn how to take time off, away from all things work, and to not feel guilty about it.

Saying no

This brings me to saying “no.” We are taught to say “yes” to every opportunity throughout our careers and, while that can certainly help us get far, it can also lead to burnout. Once you’re an attending, you’re in it for the long haul, so best to say yes to the things you are most interested in and “spark joy,” as Marie Kondo says, and say no to the things that do not make you happy and are not congruent with your overall goals. Fielder and Sihag (above) note that your division director or chief typically has a vision in mind for you within the department. It is important to communicate with leadership so that everyone is on the same page and the administrative and academic opportunities afforded to you are in alignment with your career goals going forward.

Teaching trainees

To prepare for teaching as an attending, Dr. Greco recommends starting during your own training. She suggests cataloging your study materials and notes for later reference, curating talks throughout your training, and exploring different rounding styles prior to graduation (Greco, A. CHEST Thought Leader Blog. 2021 June). To get more experience in formal speaking, Dr. Shen and colleagues encourage getting involved in resident noon conferences (Shen JZ, Memon AA, Lin C. Stroke. 2019 Sep;50[9]:e250-e252). A benefit of being a critical care attending is that you can gain experience teaching not only with the internal medicine residents but with emergency medicine, anesthesiology, and critical care advanced practice provider residents, as well.

While lecturing is one thing, teaching on service is a whole different ball game. No matter how young, fun, and relatable you think you are, you’re the boss now. You’re the giver of grades and the writer of evaluations. It is important to be self-aware of your influence and be deliberate with the environment you create on rounds and in clinic. Set expectations on day 1 so that everyone understands. Be open with what you are working on. For example, I make daily goals for myself that I share with the team before rounds. Drs. Fielder and Sihag (above) suggest sharing anecdotes from your own time in training that can help both you and your trainees remember that you were just in their shoes. Allowing yourself to be vulnerable creates a safe space in which your learners feel more comfortable doing the same.

Lastly, delegation is key. While many of us have done this since residency, Dr. Shen et al (above) suggest deliberately practicing this during fellowship. If you were the fellow who was able to handle a lot on your own, trust that your own fellows will be able to do that. Delegating to your trainees helps you improve personal and team efficiency, provides fellows with needed autonomy, and allows you to further grow into the role of attending physician.
 

Conclusion

While you may be nervous starting out, trust that you have been well trained and have the clinical knowledge and skills you need to do your job – you are ready. Get to know the staff you will be working with, your colleagues, and keep in touch with your co-trainees and mentors who have helped you along the way. Make daily goals for yourself, and make time to read and reflect so that you can continue to learn and grow. Most of all, make time for yourself, your friends, and your family, because after years of supporting you through all of your hard work, you’ve finally made it – congrats!

Dr. Greer is Assistant Professor of Medicine, Emory University Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Atlanta, GA.

As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.

For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.

Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.

As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.

For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.

Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.

As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.

For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.

Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.

As of 2019, lung cancer remained the leading cause of cancer death in the United States. In March 2021, the USPSTF updated the guidelines for lung cancer screening, increasing the number of eligible patients in order to identify malignancies in the early stages when more treatment options exist. With the growth of lung cancer screening, increasingly smaller pulmonary nodules are being identified in more peripheral locations previously thought to be unreachable with bronchoscopy. While bronchoscopy has been utilized for over a century for therapeutic interventions, the development of the fiberoptic bronchoscope in 1967 ushered in an era of evolving diagnostic functions. From the initial endobronchial and transbronchial biopsy techniques, to the introduction of endobronchial ultrasound, and now the latest navigational and robotic modalities, these advances have opened a new realm of interventions available in our diagnostic approach to lung cancer.

Bronchoscopy has become essential in the diagnosis of thoracic malignancies, providing both diagnostic and staging information in one procedural setting. By first assessing the mediastinal and hilar lymph nodes with endobronchial ultrasound and transbronchial needle aspiration, involved lymph nodes can give both diagnosis and staging information required to guide treatment. This is particularly important in the case of non-small cell lung cancer, which utilizes the TNM staging system. Through the use of convex probe endobronchial ultrasound (CP-EBUS), combined with rapid on-site evaluation (ROSE) by pathologic condition, we can more accurately target the individual lymph nodes for biopsy without the need for any additional procedures that are often more complex and invasive, such as mediastinoscopy. It is important to note the role of CP-EBUS extends beyond the lymph node assessment and can also be utilized for the evaluation of other mediastinal lesions, such as central parenchymal masses. These would otherwise be difficult to access due to the lack of a clear airway to the lesion (Argento and Puchalski. Respir Med. 2016;116:55-8).

While EBUS has improved the sampling of lymph nodes, advanced imaging technologies and subsequent increases in lung cancer screening have increased the number of lung malignancies identified in earlier stages before extension to the lymph nodes occurs. This scenario requires a direct biopsy of the primary nodule or lung mass. While CP-EBUS can be utilized for some central parenchymal lesions, peripheral nodules pose a greater challenge to the bronchoscopist as they cannot be directly visualized with the conventional bronchoscope. These lesions are amenable to traditional sampling techniques such as bronchial brushings and washings in addition to transbronchial needle aspiration and transbronchial biopsy. However, the yield for peripheral lesions is less than that for central tumors and depends on lesion size, distance from hilum, spatial positioning from bronchus, and operator experience. To help localize peripheral lesions, a separate form of endobronchial ultrasound is available that can be used in combination with fluoroscopy to target a lesion. Radial probe endobronchial ultrasound (RP-EBUS) utilizes a rotating ultrasound transducer that can be advanced either through the working channel of the bronchoscope or through a guide sheath to extend to airways beyond what the conventional bronchoscope can reach. This assists the bronchoscopist with locating the correct airway and, therefore, increases the yield of sampling techniques. The use of RP-EBUS has reported diagnostic yields of almost 85% if the ultrasound is located within the lesion, but less than 50% if adjacent to the lesion (Chen et al. Ann Am Thorac Soc. 2014;11[4]:578-82). While this improves the yield beyond that achieved with conventional bronchoscopy alone, it continues to challenge the bronchoscopist to locate an accessible airway from a series of branching bronchi that are beyond the level of direct visualization.

Due to the historical difficulty in accurately reaching peripheral lesions, alternative technologies for sampling these lesions, such as image-guided biopsies or surgical resection, were employed. While CT scan-guided biopsies traditionally have high diagnostic yields, they also carry a higher rate of complications, including pneumothorax and bleeding. This has led to a significant increase over the past 2 decades in new bronchoscopic technologies targeting safer and more accurate sampling of increasingly smaller, peripheral lesions.

Traditionally, any new technologies created were intended to be used alongside flexible fiberoptic bronchoscopy. The more recently introduced technologies, however, aim to provide a safer, more accurate procedure through virtual bronchoscopy. By obtaining CT scan images prior to the procedure, a 3D visualization is constructed of the tracheobronchial tree, allowing for directed guidance of endobronchial accessories to more distal airways. Where the bronchoscopist was previously limited in navigating the bronchial tree to the subsegmental bronchi, virtual bronchoscopy can depict the airways up to the 7th order subdivision. This is a significant improvement in airway visualization – however, only when partnered with guidance technologies can the model be accurately navigated.

One modality that is often coupled with virtual bronchoscopy to accurately reach peripheral lesions is electromagnetic navigation bronchoscopy (ENB). Multiple ENB software systems have been created and continue to be highly utilized by bronchoscopists to target peripheral lesions, as it has often been likened to a GPS for the lungs. With the addition of specific hardware components, a magnetic field is created around the patient where the sensor position can be elicited to within 1-mm accuracy. When overlaid with the CT scan images, the bronchoscopist can have real-time positioning of the probe in all three planes and guide the necessary sampling tools to the lesion of interest. The reported yields for ENB vary but have been shown to increase in the presence of specific image findings such as a positive bronchus sign – an air-filled bronchus leading into the lesion. The presence of this finding can increase the yield up to almost 75% from just under 50% in the absence of a positive bronchus sign. (Ali et al. Ann Am Thorac Soc. 2018;15[8]:978-87). However, regardless of this finding, the overall diagnostic yields for ENB continue to fall below that seen with other image-guided biopsy techniques. The procedural complications, however, are significantly less and, therefore, many physicians continue to advocate for ENB as the initial procedure in attempt to decrease risk for the patient.

The newest technology to be introduced to target peripheral lung lesions and to improve upon the shortcomings of other techniques is robotic-assisted bronchoscopy. While surgical specialties have seen success with robotic techniques over many years, the first robotic bronchoscopy system was not introduced until 2018. At present, there are two systems available: the Monarch^® system by Auris Health and the Ion Endoluminal^® System by Intuitive Surgical. These systems allow for increased bronchoscope stability, improved visualization, adjustable angulation of biopsy tools, and an improved ability to make even subtle turns in the airways. Early studies on both systems were cadaver based, but an increasing number of patient trials are now being reported or actively enrolling. Both systems have shown high rates of lesion localization, greater than 85%, with varying diagnostic yields from 69-79%. Some cadaver studies that utilized artificial tumors reported higher diagnostic yields – over 90% – but this was not seen in initial patient-based studies. (Agrawal et al. J Thorac Dis. 2020;12[6]:3279-86) More data related to the robotic-assisted bronchoscopy systems can be expected in the future as more experience is gained, but initial results are promising in the system’s ability to diagnose early lung cancers safely and accurately.

With increasing technologies and equipment available, bronchoscopy has quickly become an essential step in the diagnosis of lung cancer. While other techniques exist beyond those described here, these are some of the more widely used options currently available. It is not possible at this time to define one technology as the best tool for the diagnosis of lung cancer, as patient factors will always have to be taken into consideration to ensure safety and accuracy. However, with constantly changing technologies, the bronchoscopist now has a variety of tools available to help target previously “unreachable” lesions as we aim to decrease the historically high mortality rates of lung cancer.

Dr. Jewani and Dr. Johnson are from Loyola University Medical Center, Department of Pulmonary and Critical Care Medicine, Maywood, Illinois.


1. Agrawal, Abhinav et al. “Robotic bronchoscopy for pulmonary lesions: a review of existing technologies and clinical data.” Journal of thoracic disease vol. 12,6 (2020): 3279-3286. doi:10.21037/jtd.2020.03.35

2. Ali MS, Sethi J, Taneja A, Musani A, Maldonado F. Computed Tomography Bronchus Sign and the Diagnostic Yield of Guided Bronchoscopy for Peripheral Pulmonary Lesions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018 Aug;15(8):978-987. doi: 10.1513/AnnalsATS.201711-856OC. PMID: 29877715.

3. Argento AC, Puchalski J. Convex probe EBUS for centrally located parenchymal lesions without a bronchus sign. Respir Med. 2016 Jul;116:55-8. doi: 10.1016/j.rmed.2016.04.012. Epub 2016 Apr 29. PMID: 27296821.

4. Chen A, Chenna P, Loiselle A, Massoni J, Mayse M, Misselhorn D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions. A 5-year institutional experience. Ann Am Thorac Soc. 2014 May;11(4):578-82. doi: 10.1513/AnnalsATS.201311-384OC. PMID: 24635641.
 

As of 2019, lung cancer remained the leading cause of cancer death in the United States. In March 2021, the USPSTF updated the guidelines for lung cancer screening, increasing the number of eligible patients in order to identify malignancies in the early stages when more treatment options exist. With the growth of lung cancer screening, increasingly smaller pulmonary nodules are being identified in more peripheral locations previously thought to be unreachable with bronchoscopy. While bronchoscopy has been utilized for over a century for therapeutic interventions, the development of the fiberoptic bronchoscope in 1967 ushered in an era of evolving diagnostic functions. From the initial endobronchial and transbronchial biopsy techniques, to the introduction of endobronchial ultrasound, and now the latest navigational and robotic modalities, these advances have opened a new realm of interventions available in our diagnostic approach to lung cancer.

Bronchoscopy has become essential in the diagnosis of thoracic malignancies, providing both diagnostic and staging information in one procedural setting. By first assessing the mediastinal and hilar lymph nodes with endobronchial ultrasound and transbronchial needle aspiration, involved lymph nodes can give both diagnosis and staging information required to guide treatment. This is particularly important in the case of non-small cell lung cancer, which utilizes the TNM staging system. Through the use of convex probe endobronchial ultrasound (CP-EBUS), combined with rapid on-site evaluation (ROSE) by pathologic condition, we can more accurately target the individual lymph nodes for biopsy without the need for any additional procedures that are often more complex and invasive, such as mediastinoscopy. It is important to note the role of CP-EBUS extends beyond the lymph node assessment and can also be utilized for the evaluation of other mediastinal lesions, such as central parenchymal masses. These would otherwise be difficult to access due to the lack of a clear airway to the lesion (Argento and Puchalski. Respir Med. 2016;116:55-8).

While EBUS has improved the sampling of lymph nodes, advanced imaging technologies and subsequent increases in lung cancer screening have increased the number of lung malignancies identified in earlier stages before extension to the lymph nodes occurs. This scenario requires a direct biopsy of the primary nodule or lung mass. While CP-EBUS can be utilized for some central parenchymal lesions, peripheral nodules pose a greater challenge to the bronchoscopist as they cannot be directly visualized with the conventional bronchoscope. These lesions are amenable to traditional sampling techniques such as bronchial brushings and washings in addition to transbronchial needle aspiration and transbronchial biopsy. However, the yield for peripheral lesions is less than that for central tumors and depends on lesion size, distance from hilum, spatial positioning from bronchus, and operator experience. To help localize peripheral lesions, a separate form of endobronchial ultrasound is available that can be used in combination with fluoroscopy to target a lesion. Radial probe endobronchial ultrasound (RP-EBUS) utilizes a rotating ultrasound transducer that can be advanced either through the working channel of the bronchoscope or through a guide sheath to extend to airways beyond what the conventional bronchoscope can reach. This assists the bronchoscopist with locating the correct airway and, therefore, increases the yield of sampling techniques. The use of RP-EBUS has reported diagnostic yields of almost 85% if the ultrasound is located within the lesion, but less than 50% if adjacent to the lesion (Chen et al. Ann Am Thorac Soc. 2014;11[4]:578-82). While this improves the yield beyond that achieved with conventional bronchoscopy alone, it continues to challenge the bronchoscopist to locate an accessible airway from a series of branching bronchi that are beyond the level of direct visualization.

Due to the historical difficulty in accurately reaching peripheral lesions, alternative technologies for sampling these lesions, such as image-guided biopsies or surgical resection, were employed. While CT scan-guided biopsies traditionally have high diagnostic yields, they also carry a higher rate of complications, including pneumothorax and bleeding. This has led to a significant increase over the past 2 decades in new bronchoscopic technologies targeting safer and more accurate sampling of increasingly smaller, peripheral lesions.

Traditionally, any new technologies created were intended to be used alongside flexible fiberoptic bronchoscopy. The more recently introduced technologies, however, aim to provide a safer, more accurate procedure through virtual bronchoscopy. By obtaining CT scan images prior to the procedure, a 3D visualization is constructed of the tracheobronchial tree, allowing for directed guidance of endobronchial accessories to more distal airways. Where the bronchoscopist was previously limited in navigating the bronchial tree to the subsegmental bronchi, virtual bronchoscopy can depict the airways up to the 7th order subdivision. This is a significant improvement in airway visualization – however, only when partnered with guidance technologies can the model be accurately navigated.

One modality that is often coupled with virtual bronchoscopy to accurately reach peripheral lesions is electromagnetic navigation bronchoscopy (ENB). Multiple ENB software systems have been created and continue to be highly utilized by bronchoscopists to target peripheral lesions, as it has often been likened to a GPS for the lungs. With the addition of specific hardware components, a magnetic field is created around the patient where the sensor position can be elicited to within 1-mm accuracy. When overlaid with the CT scan images, the bronchoscopist can have real-time positioning of the probe in all three planes and guide the necessary sampling tools to the lesion of interest. The reported yields for ENB vary but have been shown to increase in the presence of specific image findings such as a positive bronchus sign – an air-filled bronchus leading into the lesion. The presence of this finding can increase the yield up to almost 75% from just under 50% in the absence of a positive bronchus sign. (Ali et al. Ann Am Thorac Soc. 2018;15[8]:978-87). However, regardless of this finding, the overall diagnostic yields for ENB continue to fall below that seen with other image-guided biopsy techniques. The procedural complications, however, are significantly less and, therefore, many physicians continue to advocate for ENB as the initial procedure in attempt to decrease risk for the patient.

The newest technology to be introduced to target peripheral lung lesions and to improve upon the shortcomings of other techniques is robotic-assisted bronchoscopy. While surgical specialties have seen success with robotic techniques over many years, the first robotic bronchoscopy system was not introduced until 2018. At present, there are two systems available: the Monarch^® system by Auris Health and the Ion Endoluminal^® System by Intuitive Surgical. These systems allow for increased bronchoscope stability, improved visualization, adjustable angulation of biopsy tools, and an improved ability to make even subtle turns in the airways. Early studies on both systems were cadaver based, but an increasing number of patient trials are now being reported or actively enrolling. Both systems have shown high rates of lesion localization, greater than 85%, with varying diagnostic yields from 69-79%. Some cadaver studies that utilized artificial tumors reported higher diagnostic yields – over 90% – but this was not seen in initial patient-based studies. (Agrawal et al. J Thorac Dis. 2020;12[6]:3279-86) More data related to the robotic-assisted bronchoscopy systems can be expected in the future as more experience is gained, but initial results are promising in the system’s ability to diagnose early lung cancers safely and accurately.

With increasing technologies and equipment available, bronchoscopy has quickly become an essential step in the diagnosis of lung cancer. While other techniques exist beyond those described here, these are some of the more widely used options currently available. It is not possible at this time to define one technology as the best tool for the diagnosis of lung cancer, as patient factors will always have to be taken into consideration to ensure safety and accuracy. However, with constantly changing technologies, the bronchoscopist now has a variety of tools available to help target previously “unreachable” lesions as we aim to decrease the historically high mortality rates of lung cancer.

Dr. Jewani and Dr. Johnson are from Loyola University Medical Center, Department of Pulmonary and Critical Care Medicine, Maywood, Illinois.


1. Agrawal, Abhinav et al. “Robotic bronchoscopy for pulmonary lesions: a review of existing technologies and clinical data.” Journal of thoracic disease vol. 12,6 (2020): 3279-3286. doi:10.21037/jtd.2020.03.35

2. Ali MS, Sethi J, Taneja A, Musani A, Maldonado F. Computed Tomography Bronchus Sign and the Diagnostic Yield of Guided Bronchoscopy for Peripheral Pulmonary Lesions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018 Aug;15(8):978-987. doi: 10.1513/AnnalsATS.201711-856OC. PMID: 29877715.

3. Argento AC, Puchalski J. Convex probe EBUS for centrally located parenchymal lesions without a bronchus sign. Respir Med. 2016 Jul;116:55-8. doi: 10.1016/j.rmed.2016.04.012. Epub 2016 Apr 29. PMID: 27296821.

4. Chen A, Chenna P, Loiselle A, Massoni J, Mayse M, Misselhorn D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions. A 5-year institutional experience. Ann Am Thorac Soc. 2014 May;11(4):578-82. doi: 10.1513/AnnalsATS.201311-384OC. PMID: 24635641.
 

As of 2019, lung cancer remained the leading cause of cancer death in the United States. In March 2021, the USPSTF updated the guidelines for lung cancer screening, increasing the number of eligible patients in order to identify malignancies in the early stages when more treatment options exist. With the growth of lung cancer screening, increasingly smaller pulmonary nodules are being identified in more peripheral locations previously thought to be unreachable with bronchoscopy. While bronchoscopy has been utilized for over a century for therapeutic interventions, the development of the fiberoptic bronchoscope in 1967 ushered in an era of evolving diagnostic functions. From the initial endobronchial and transbronchial biopsy techniques, to the introduction of endobronchial ultrasound, and now the latest navigational and robotic modalities, these advances have opened a new realm of interventions available in our diagnostic approach to lung cancer.

Bronchoscopy has become essential in the diagnosis of thoracic malignancies, providing both diagnostic and staging information in one procedural setting. By first assessing the mediastinal and hilar lymph nodes with endobronchial ultrasound and transbronchial needle aspiration, involved lymph nodes can give both diagnosis and staging information required to guide treatment. This is particularly important in the case of non-small cell lung cancer, which utilizes the TNM staging system. Through the use of convex probe endobronchial ultrasound (CP-EBUS), combined with rapid on-site evaluation (ROSE) by pathologic condition, we can more accurately target the individual lymph nodes for biopsy without the need for any additional procedures that are often more complex and invasive, such as mediastinoscopy. It is important to note the role of CP-EBUS extends beyond the lymph node assessment and can also be utilized for the evaluation of other mediastinal lesions, such as central parenchymal masses. These would otherwise be difficult to access due to the lack of a clear airway to the lesion (Argento and Puchalski. Respir Med. 2016;116:55-8).

While EBUS has improved the sampling of lymph nodes, advanced imaging technologies and subsequent increases in lung cancer screening have increased the number of lung malignancies identified in earlier stages before extension to the lymph nodes occurs. This scenario requires a direct biopsy of the primary nodule or lung mass. While CP-EBUS can be utilized for some central parenchymal lesions, peripheral nodules pose a greater challenge to the bronchoscopist as they cannot be directly visualized with the conventional bronchoscope. These lesions are amenable to traditional sampling techniques such as bronchial brushings and washings in addition to transbronchial needle aspiration and transbronchial biopsy. However, the yield for peripheral lesions is less than that for central tumors and depends on lesion size, distance from hilum, spatial positioning from bronchus, and operator experience. To help localize peripheral lesions, a separate form of endobronchial ultrasound is available that can be used in combination with fluoroscopy to target a lesion. Radial probe endobronchial ultrasound (RP-EBUS) utilizes a rotating ultrasound transducer that can be advanced either through the working channel of the bronchoscope or through a guide sheath to extend to airways beyond what the conventional bronchoscope can reach. This assists the bronchoscopist with locating the correct airway and, therefore, increases the yield of sampling techniques. The use of RP-EBUS has reported diagnostic yields of almost 85% if the ultrasound is located within the lesion, but less than 50% if adjacent to the lesion (Chen et al. Ann Am Thorac Soc. 2014;11[4]:578-82). While this improves the yield beyond that achieved with conventional bronchoscopy alone, it continues to challenge the bronchoscopist to locate an accessible airway from a series of branching bronchi that are beyond the level of direct visualization.

Due to the historical difficulty in accurately reaching peripheral lesions, alternative technologies for sampling these lesions, such as image-guided biopsies or surgical resection, were employed. While CT scan-guided biopsies traditionally have high diagnostic yields, they also carry a higher rate of complications, including pneumothorax and bleeding. This has led to a significant increase over the past 2 decades in new bronchoscopic technologies targeting safer and more accurate sampling of increasingly smaller, peripheral lesions.

Traditionally, any new technologies created were intended to be used alongside flexible fiberoptic bronchoscopy. The more recently introduced technologies, however, aim to provide a safer, more accurate procedure through virtual bronchoscopy. By obtaining CT scan images prior to the procedure, a 3D visualization is constructed of the tracheobronchial tree, allowing for directed guidance of endobronchial accessories to more distal airways. Where the bronchoscopist was previously limited in navigating the bronchial tree to the subsegmental bronchi, virtual bronchoscopy can depict the airways up to the 7th order subdivision. This is a significant improvement in airway visualization – however, only when partnered with guidance technologies can the model be accurately navigated.

One modality that is often coupled with virtual bronchoscopy to accurately reach peripheral lesions is electromagnetic navigation bronchoscopy (ENB). Multiple ENB software systems have been created and continue to be highly utilized by bronchoscopists to target peripheral lesions, as it has often been likened to a GPS for the lungs. With the addition of specific hardware components, a magnetic field is created around the patient where the sensor position can be elicited to within 1-mm accuracy. When overlaid with the CT scan images, the bronchoscopist can have real-time positioning of the probe in all three planes and guide the necessary sampling tools to the lesion of interest. The reported yields for ENB vary but have been shown to increase in the presence of specific image findings such as a positive bronchus sign – an air-filled bronchus leading into the lesion. The presence of this finding can increase the yield up to almost 75% from just under 50% in the absence of a positive bronchus sign. (Ali et al. Ann Am Thorac Soc. 2018;15[8]:978-87). However, regardless of this finding, the overall diagnostic yields for ENB continue to fall below that seen with other image-guided biopsy techniques. The procedural complications, however, are significantly less and, therefore, many physicians continue to advocate for ENB as the initial procedure in attempt to decrease risk for the patient.

The newest technology to be introduced to target peripheral lung lesions and to improve upon the shortcomings of other techniques is robotic-assisted bronchoscopy. While surgical specialties have seen success with robotic techniques over many years, the first robotic bronchoscopy system was not introduced until 2018. At present, there are two systems available: the Monarch^® system by Auris Health and the Ion Endoluminal^® System by Intuitive Surgical. These systems allow for increased bronchoscope stability, improved visualization, adjustable angulation of biopsy tools, and an improved ability to make even subtle turns in the airways. Early studies on both systems were cadaver based, but an increasing number of patient trials are now being reported or actively enrolling. Both systems have shown high rates of lesion localization, greater than 85%, with varying diagnostic yields from 69-79%. Some cadaver studies that utilized artificial tumors reported higher diagnostic yields – over 90% – but this was not seen in initial patient-based studies. (Agrawal et al. J Thorac Dis. 2020;12[6]:3279-86) More data related to the robotic-assisted bronchoscopy systems can be expected in the future as more experience is gained, but initial results are promising in the system’s ability to diagnose early lung cancers safely and accurately.

With increasing technologies and equipment available, bronchoscopy has quickly become an essential step in the diagnosis of lung cancer. While other techniques exist beyond those described here, these are some of the more widely used options currently available. It is not possible at this time to define one technology as the best tool for the diagnosis of lung cancer, as patient factors will always have to be taken into consideration to ensure safety and accuracy. However, with constantly changing technologies, the bronchoscopist now has a variety of tools available to help target previously “unreachable” lesions as we aim to decrease the historically high mortality rates of lung cancer.

Dr. Jewani and Dr. Johnson are from Loyola University Medical Center, Department of Pulmonary and Critical Care Medicine, Maywood, Illinois.


1. Agrawal, Abhinav et al. “Robotic bronchoscopy for pulmonary lesions: a review of existing technologies and clinical data.” Journal of thoracic disease vol. 12,6 (2020): 3279-3286. doi:10.21037/jtd.2020.03.35

2. Ali MS, Sethi J, Taneja A, Musani A, Maldonado F. Computed Tomography Bronchus Sign and the Diagnostic Yield of Guided Bronchoscopy for Peripheral Pulmonary Lesions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018 Aug;15(8):978-987. doi: 10.1513/AnnalsATS.201711-856OC. PMID: 29877715.

3. Argento AC, Puchalski J. Convex probe EBUS for centrally located parenchymal lesions without a bronchus sign. Respir Med. 2016 Jul;116:55-8. doi: 10.1016/j.rmed.2016.04.012. Epub 2016 Apr 29. PMID: 27296821.

4. Chen A, Chenna P, Loiselle A, Massoni J, Mayse M, Misselhorn D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions. A 5-year institutional experience. Ann Am Thorac Soc. 2014 May;11(4):578-82. doi: 10.1513/AnnalsATS.201311-384OC. PMID: 24635641.