CHEST Physician

Over a year has passed since the first case of COVID-19 was reported in the United States, with over 114 million cases now reported worldwide, and over 2.5 million deaths at the time of this writing (Dong E, et al. Lancet Infect Dis. doi: 10.1016/S1473-3099[20]30120-1). While our vaccination efforts here in the United States have provided a much-needed glimmer of hope, it has been bittersweet, as we recently surpassed the grim milestone of 500,000 COVID-19-related deaths.

The infectious nature of SARS-CoV-2, coupled with the lack of adequate PPE early in the pandemic, led to radical changes in most hospital visitor policies. Rather than welcoming families into the care setting as we have been accustomed, we were forced to restrict access. While well-intentioned, the impact of this on patients, their families – and as we later learned, ourselves – has been devastating. Patients found themselves alone in an unfamiliar environment, infected with a disease there was no effective treatment for, hearing dismal news regarding inpatient and ICU mortality rates on news networks, and families could not see for themselves how their loved ones were progressing in their hospital course.
 

The impact on patient-centered care

The impact of this pandemic on patients and health care providers alike cannot be overstated. Arguably, one of the greatest challenges created by COVID-19 has been its direct assault on the core values of patient-centered care that we have spent decades striving to promote and embody.

Since its identification as a quality gap by the Institute of Medicine in 2001, the definition of patient-centered care has been tweaked over the past 20 years (Institute of Medicine (IOM). Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, D.C: National Academy Press; 2001). Most frameworks include the active participation of patients and their families as part of the health care team, encouraging and facilitating the presence of family members in the care setting, and focusing on patients’ physical comfort and emotional well-being as fundamental tenets of patient centeredness (NEJM Catalyst: What is Patient-Centered Care? Explore the definition, benefits, and examples of patient-centered care. How does patient-centered care translate to new delivery models? January 1,2017).

Families, the “F” in the ABCDEF Bundle, have been recognized as an integral part of care in the ICU setting (Ely EW. Crit Care Med. 2017;45[2]:321). While engagement of family members began with our recognition of their role in emotionally supporting patients and efforts to improve communication, we have also seen the impact of family participation on reducing ICU delirium through frequent re-orientation and encouragement of early mobility (McKenzie J, et al. Australas J Ageing. 2020;39:21). In fact, a recent study has suggested that family members could play an even more active role in detecting and assessing ICU delirium using objective assessment tools (Fiest K, et al. Crit Care Med. 2020;48[7]:954). Post-ICU PTSD has been well described in both ICU survivors as well as in their family members, with evidence that family participation in care of patients during their ICU stay leads to its reduction (Amass TH, et al. Crit Care Med. 2020[Feb];48[2]:176).
 

The emotional toll

Comforting patients and families in times of distress and suffering is something that comes naturally to many in critical care, and our training further improves our ability to do this effectively. No amount of training, however, could have prepared us for the degree and volume of suffering we bore witness to this past year and the resulting moral injury many are still dealing with. We were present for families’ most intimate moments, holding phones and tablets up to patients so their families could say their goodbyes, listening to the “I love yous,” “I’ll miss yous,” “I’m sorrys,” and “Please don’t gos.” Nurses held patients’ hands as they took their last breaths so they wouldn’t die alone and worked to move husbands and wives into the same room so they could be together in their final moments. Entrenched in each of our identities is the role of healer, and we found ourselves questioning our effectiveness in rising to meet suffering on a scale we had never seen before. Little did we understand that while our paradigms were reinforcing the benefits of patient-centered care for patients and their families, that framework was also serving to facilitate our role as healers – that without it, we all suffer.

Rising to the challenge

These unprecedented circumstances led to creative efforts to bridge some of these barriers. Health systems created photo lanyards that providers wore over their PPE so patients could identify their health care team and connect with them on a more human level. Video conferencing technology was brought to the patient bedside using smartphones and tablets to assist them in communicating with their families. Doctors and nurses coordinated multiple calls throughout the day to ensure families felt included in the care plans and were always abreast of any new developments.

All these initiatives were our way of attempting to alleviate some of the suffering we were witnessing, and in some ways felt complicit in. It is in hindsight that we can look back and question if we could have done things differently. We treated family as visitors, when in fact, they are fundamental members of the care team who play an active and critical role in patient care. This was, in part, driven by national unpreparedness when it came to PPE supplies, in addition to misinformation and inconsistent messaging early in the pandemic with regards to the mechanism of transmission of disease from various health organizations. While we did our best given the circumstances, we must not allow this experience to lead us away from the tenets we know to be essential to patient, family, and health care provider well-being.

All in health care met the call to action – nurses, physicians, advanced practice providers, respiratory therapists, nutritionists, pharmacists, physical therapists, patient transporters, environmental service workers, and all others who kept our hospitals and patient care facilities open through this pandemic and embarked on what amounted to a collective, global, ongoing “code-blue alert,” resuscitating patient after patient, hotspot after hotspot, region after region, and country after country. We expanded hospital bed capacities, created ICU beds where there were none, developed novel process protocols, and learned in real time what seemed to help (or not) in treating this novel disease, all while participating in incredible international scientific collaboration and information sharing that has contributed in getting the collective “us” through this first year of the pandemic. We did what we were trained and called to do.
 

Preparing for the future

There will inevitably be another public health crisis, and we must advocate for better preparedness next time, insisting on overall stronger public health systems and pandemic preparedness. We must address our PPE stores and supply chains. We must have disaster preparedness plans that go beyond the scope of mass casualty events and bioterrorism. Beyond physical recovery, we must tend to the factors that impact patients’ long-term recovery, with attention to emotional and psychological well-being. We must advocate for all of this now, while the memories are fresh and before the impact of this collective suffering begins to fade. It can never again be acceptable to exclude families from the health care setting. We must advocate for our patients and for the resources, systems, processes, and support that will allow us to do better.

Dr. Hegab is Associate Director, Pulmonary Hypertension Program, Medical Director, Pulmonary Embolism Response Team, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital; and Assistant Professor, Wayne State University School of Medicine, Detroit.

Over a year has passed since the first case of COVID-19 was reported in the United States, with over 114 million cases now reported worldwide, and over 2.5 million deaths at the time of this writing (Dong E, et al. Lancet Infect Dis. doi: 10.1016/S1473-3099[20]30120-1). While our vaccination efforts here in the United States have provided a much-needed glimmer of hope, it has been bittersweet, as we recently surpassed the grim milestone of 500,000 COVID-19-related deaths.

The infectious nature of SARS-CoV-2, coupled with the lack of adequate PPE early in the pandemic, led to radical changes in most hospital visitor policies. Rather than welcoming families into the care setting as we have been accustomed, we were forced to restrict access. While well-intentioned, the impact of this on patients, their families – and as we later learned, ourselves – has been devastating. Patients found themselves alone in an unfamiliar environment, infected with a disease there was no effective treatment for, hearing dismal news regarding inpatient and ICU mortality rates on news networks, and families could not see for themselves how their loved ones were progressing in their hospital course.
 

The impact on patient-centered care

The impact of this pandemic on patients and health care providers alike cannot be overstated. Arguably, one of the greatest challenges created by COVID-19 has been its direct assault on the core values of patient-centered care that we have spent decades striving to promote and embody.

Since its identification as a quality gap by the Institute of Medicine in 2001, the definition of patient-centered care has been tweaked over the past 20 years (Institute of Medicine (IOM). Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, D.C: National Academy Press; 2001). Most frameworks include the active participation of patients and their families as part of the health care team, encouraging and facilitating the presence of family members in the care setting, and focusing on patients’ physical comfort and emotional well-being as fundamental tenets of patient centeredness (NEJM Catalyst: What is Patient-Centered Care? Explore the definition, benefits, and examples of patient-centered care. How does patient-centered care translate to new delivery models? January 1,2017).

Families, the “F” in the ABCDEF Bundle, have been recognized as an integral part of care in the ICU setting (Ely EW. Crit Care Med. 2017;45[2]:321). While engagement of family members began with our recognition of their role in emotionally supporting patients and efforts to improve communication, we have also seen the impact of family participation on reducing ICU delirium through frequent re-orientation and encouragement of early mobility (McKenzie J, et al. Australas J Ageing. 2020;39:21). In fact, a recent study has suggested that family members could play an even more active role in detecting and assessing ICU delirium using objective assessment tools (Fiest K, et al. Crit Care Med. 2020;48[7]:954). Post-ICU PTSD has been well described in both ICU survivors as well as in their family members, with evidence that family participation in care of patients during their ICU stay leads to its reduction (Amass TH, et al. Crit Care Med. 2020[Feb];48[2]:176).
 

The emotional toll

Comforting patients and families in times of distress and suffering is something that comes naturally to many in critical care, and our training further improves our ability to do this effectively. No amount of training, however, could have prepared us for the degree and volume of suffering we bore witness to this past year and the resulting moral injury many are still dealing with. We were present for families’ most intimate moments, holding phones and tablets up to patients so their families could say their goodbyes, listening to the “I love yous,” “I’ll miss yous,” “I’m sorrys,” and “Please don’t gos.” Nurses held patients’ hands as they took their last breaths so they wouldn’t die alone and worked to move husbands and wives into the same room so they could be together in their final moments. Entrenched in each of our identities is the role of healer, and we found ourselves questioning our effectiveness in rising to meet suffering on a scale we had never seen before. Little did we understand that while our paradigms were reinforcing the benefits of patient-centered care for patients and their families, that framework was also serving to facilitate our role as healers – that without it, we all suffer.

Rising to the challenge

These unprecedented circumstances led to creative efforts to bridge some of these barriers. Health systems created photo lanyards that providers wore over their PPE so patients could identify their health care team and connect with them on a more human level. Video conferencing technology was brought to the patient bedside using smartphones and tablets to assist them in communicating with their families. Doctors and nurses coordinated multiple calls throughout the day to ensure families felt included in the care plans and were always abreast of any new developments.

All these initiatives were our way of attempting to alleviate some of the suffering we were witnessing, and in some ways felt complicit in. It is in hindsight that we can look back and question if we could have done things differently. We treated family as visitors, when in fact, they are fundamental members of the care team who play an active and critical role in patient care. This was, in part, driven by national unpreparedness when it came to PPE supplies, in addition to misinformation and inconsistent messaging early in the pandemic with regards to the mechanism of transmission of disease from various health organizations. While we did our best given the circumstances, we must not allow this experience to lead us away from the tenets we know to be essential to patient, family, and health care provider well-being.

All in health care met the call to action – nurses, physicians, advanced practice providers, respiratory therapists, nutritionists, pharmacists, physical therapists, patient transporters, environmental service workers, and all others who kept our hospitals and patient care facilities open through this pandemic and embarked on what amounted to a collective, global, ongoing “code-blue alert,” resuscitating patient after patient, hotspot after hotspot, region after region, and country after country. We expanded hospital bed capacities, created ICU beds where there were none, developed novel process protocols, and learned in real time what seemed to help (or not) in treating this novel disease, all while participating in incredible international scientific collaboration and information sharing that has contributed in getting the collective “us” through this first year of the pandemic. We did what we were trained and called to do.
 

Preparing for the future

There will inevitably be another public health crisis, and we must advocate for better preparedness next time, insisting on overall stronger public health systems and pandemic preparedness. We must address our PPE stores and supply chains. We must have disaster preparedness plans that go beyond the scope of mass casualty events and bioterrorism. Beyond physical recovery, we must tend to the factors that impact patients’ long-term recovery, with attention to emotional and psychological well-being. We must advocate for all of this now, while the memories are fresh and before the impact of this collective suffering begins to fade. It can never again be acceptable to exclude families from the health care setting. We must advocate for our patients and for the resources, systems, processes, and support that will allow us to do better.

Dr. Hegab is Associate Director, Pulmonary Hypertension Program, Medical Director, Pulmonary Embolism Response Team, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital; and Assistant Professor, Wayne State University School of Medicine, Detroit.

Over a year has passed since the first case of COVID-19 was reported in the United States, with over 114 million cases now reported worldwide, and over 2.5 million deaths at the time of this writing (Dong E, et al. Lancet Infect Dis. doi: 10.1016/S1473-3099[20]30120-1). While our vaccination efforts here in the United States have provided a much-needed glimmer of hope, it has been bittersweet, as we recently surpassed the grim milestone of 500,000 COVID-19-related deaths.

The infectious nature of SARS-CoV-2, coupled with the lack of adequate PPE early in the pandemic, led to radical changes in most hospital visitor policies. Rather than welcoming families into the care setting as we have been accustomed, we were forced to restrict access. While well-intentioned, the impact of this on patients, their families – and as we later learned, ourselves – has been devastating. Patients found themselves alone in an unfamiliar environment, infected with a disease there was no effective treatment for, hearing dismal news regarding inpatient and ICU mortality rates on news networks, and families could not see for themselves how their loved ones were progressing in their hospital course.
 

The impact on patient-centered care

The impact of this pandemic on patients and health care providers alike cannot be overstated. Arguably, one of the greatest challenges created by COVID-19 has been its direct assault on the core values of patient-centered care that we have spent decades striving to promote and embody.

Since its identification as a quality gap by the Institute of Medicine in 2001, the definition of patient-centered care has been tweaked over the past 20 years (Institute of Medicine (IOM). Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, D.C: National Academy Press; 2001). Most frameworks include the active participation of patients and their families as part of the health care team, encouraging and facilitating the presence of family members in the care setting, and focusing on patients’ physical comfort and emotional well-being as fundamental tenets of patient centeredness (NEJM Catalyst: What is Patient-Centered Care? Explore the definition, benefits, and examples of patient-centered care. How does patient-centered care translate to new delivery models? January 1,2017).

Families, the “F” in the ABCDEF Bundle, have been recognized as an integral part of care in the ICU setting (Ely EW. Crit Care Med. 2017;45[2]:321). While engagement of family members began with our recognition of their role in emotionally supporting patients and efforts to improve communication, we have also seen the impact of family participation on reducing ICU delirium through frequent re-orientation and encouragement of early mobility (McKenzie J, et al. Australas J Ageing. 2020;39:21). In fact, a recent study has suggested that family members could play an even more active role in detecting and assessing ICU delirium using objective assessment tools (Fiest K, et al. Crit Care Med. 2020;48[7]:954). Post-ICU PTSD has been well described in both ICU survivors as well as in their family members, with evidence that family participation in care of patients during their ICU stay leads to its reduction (Amass TH, et al. Crit Care Med. 2020[Feb];48[2]:176).
 

The emotional toll

Comforting patients and families in times of distress and suffering is something that comes naturally to many in critical care, and our training further improves our ability to do this effectively. No amount of training, however, could have prepared us for the degree and volume of suffering we bore witness to this past year and the resulting moral injury many are still dealing with. We were present for families’ most intimate moments, holding phones and tablets up to patients so their families could say their goodbyes, listening to the “I love yous,” “I’ll miss yous,” “I’m sorrys,” and “Please don’t gos.” Nurses held patients’ hands as they took their last breaths so they wouldn’t die alone and worked to move husbands and wives into the same room so they could be together in their final moments. Entrenched in each of our identities is the role of healer, and we found ourselves questioning our effectiveness in rising to meet suffering on a scale we had never seen before. Little did we understand that while our paradigms were reinforcing the benefits of patient-centered care for patients and their families, that framework was also serving to facilitate our role as healers – that without it, we all suffer.

Rising to the challenge

These unprecedented circumstances led to creative efforts to bridge some of these barriers. Health systems created photo lanyards that providers wore over their PPE so patients could identify their health care team and connect with them on a more human level. Video conferencing technology was brought to the patient bedside using smartphones and tablets to assist them in communicating with their families. Doctors and nurses coordinated multiple calls throughout the day to ensure families felt included in the care plans and were always abreast of any new developments.

All these initiatives were our way of attempting to alleviate some of the suffering we were witnessing, and in some ways felt complicit in. It is in hindsight that we can look back and question if we could have done things differently. We treated family as visitors, when in fact, they are fundamental members of the care team who play an active and critical role in patient care. This was, in part, driven by national unpreparedness when it came to PPE supplies, in addition to misinformation and inconsistent messaging early in the pandemic with regards to the mechanism of transmission of disease from various health organizations. While we did our best given the circumstances, we must not allow this experience to lead us away from the tenets we know to be essential to patient, family, and health care provider well-being.

All in health care met the call to action – nurses, physicians, advanced practice providers, respiratory therapists, nutritionists, pharmacists, physical therapists, patient transporters, environmental service workers, and all others who kept our hospitals and patient care facilities open through this pandemic and embarked on what amounted to a collective, global, ongoing “code-blue alert,” resuscitating patient after patient, hotspot after hotspot, region after region, and country after country. We expanded hospital bed capacities, created ICU beds where there were none, developed novel process protocols, and learned in real time what seemed to help (or not) in treating this novel disease, all while participating in incredible international scientific collaboration and information sharing that has contributed in getting the collective “us” through this first year of the pandemic. We did what we were trained and called to do.
 

Preparing for the future

There will inevitably be another public health crisis, and we must advocate for better preparedness next time, insisting on overall stronger public health systems and pandemic preparedness. We must address our PPE stores and supply chains. We must have disaster preparedness plans that go beyond the scope of mass casualty events and bioterrorism. Beyond physical recovery, we must tend to the factors that impact patients’ long-term recovery, with attention to emotional and psychological well-being. We must advocate for all of this now, while the memories are fresh and before the impact of this collective suffering begins to fade. It can never again be acceptable to exclude families from the health care setting. We must advocate for our patients and for the resources, systems, processes, and support that will allow us to do better.

Dr. Hegab is Associate Director, Pulmonary Hypertension Program, Medical Director, Pulmonary Embolism Response Team, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital; and Assistant Professor, Wayne State University School of Medicine, Detroit.

The relationship between asthma and cardiovascular disease: An examination of the Framingham offspring study. By Dr M. Pollevick, et al.

Projecting long-term health and economic burden of chronic obstructive pulmonary disease in the United States. By Dr. Z. Zafari, et al.



How I do it: Dosing fluids in early septic shock. By Dr. D. Chaudhuri, et al.



Essential components of an interstitial lung disease clinic: Results from a Delphi survey and patient focus group analysis. By Dr. B. A. Graney, et al.



Change: Leadership essentials for chest medicine professionals. By Dr. J. Stoller, et al.



Race correction and spirometry: Why history matters. By Dr. L. Braun.

The relationship between asthma and cardiovascular disease: An examination of the Framingham offspring study. By Dr M. Pollevick, et al.

Projecting long-term health and economic burden of chronic obstructive pulmonary disease in the United States. By Dr. Z. Zafari, et al.



How I do it: Dosing fluids in early septic shock. By Dr. D. Chaudhuri, et al.



Essential components of an interstitial lung disease clinic: Results from a Delphi survey and patient focus group analysis. By Dr. B. A. Graney, et al.



Change: Leadership essentials for chest medicine professionals. By Dr. J. Stoller, et al.



Race correction and spirometry: Why history matters. By Dr. L. Braun.

The relationship between asthma and cardiovascular disease: An examination of the Framingham offspring study. By Dr M. Pollevick, et al.

Projecting long-term health and economic burden of chronic obstructive pulmonary disease in the United States. By Dr. Z. Zafari, et al.



How I do it: Dosing fluids in early septic shock. By Dr. D. Chaudhuri, et al.



Essential components of an interstitial lung disease clinic: Results from a Delphi survey and patient focus group analysis. By Dr. B. A. Graney, et al.



Change: Leadership essentials for chest medicine professionals. By Dr. J. Stoller, et al.



Race correction and spirometry: Why history matters. By Dr. L. Braun.

National Asthma Education and Prevention Program (NAEPP) published its last Expert Panel Report in 2007. Since that time, substantial progress has been made in understanding the pathophysiology and treatment of asthma. A new report has provided a much-needed update in the evaluation and management of asthma. It focuses on several priority topics jointly decided upon by the National Heart, Lung, and Blood Institute (NHLBI) Advisory Council Asthma Expert Working Group, the National Asthma Education and Prevention Program (NAEPP) participant organizations, and the public in 2015. These topics include the role of fractional exhaled nitric oxide (FeNO), allergen mitigation, intermittent inhaled corticosteroids (ICS), long-acting muscarinic agents (LAMA), immunotherapy, and bronchial thermoplasty (BT) in asthma management. This document did not include the subsequent new developments in the role of biologics in asthma. The following is a summary of the recommendations made in the 2020 Focused Updates to the Asthma Management Guidelines.¹

FeNO measurement is recommended to aid in asthma diagnosis and monitoring and to assist in ICS medication titration in individuals with asthma who are 5 years and older. The panel recommends that clinicians use FeNO levels, in conjunction with other relevant clinical data such as spirometry and asthma control questionnaires, for medical decision making. Similarly, when using FeNO to guide therapeutic changes in the ICS dose, the panel advises making changes based upon frequent measurements as a part of longitudinal assessment rather than one single measurement, as several factors can influence an FeNO measurement. Studies have demonstrated that a strategy that incorporates FeNO measurements into a treatment algorithm can reduce the risk of exacerbations; however, this has not been shown to reduce hospitalizations or quality of life.²

Allergen mitigation interventions, which can be used in individuals of all ages, are only recommended for those who have symptoms related to specific indoor aeroallergens exposure. This can be confirmed by skin testing or specific IgE in the appropriate clinical setting if specific allergen testing is not readily available. While most recommendations focus on using a multicomponent approach to allergen mitigation (ie, dust mite covers, HEPA filters, air purifiers, carpet removal, mold remediation, pest or pest removal, etc), pest removal was the only single-component approach that was deemed effective. Dust mite covers alone are unlikely to lead to significant improvement if not paired with additional mitigation strategies; however, note that there was low certainty about these recommendations. Ultimately, allergen mitigation should focus on addressing those identified triggers resulting in poor control of asthma. Simultaneously, the clinician should consider the resources and costs associated with some of these interventions.

The panel has recommended using ICS therapy for on-demand (prn) usage, even in those with mild persistent asthma, recognizing that earlier and more frequent on-demand ICS usage results in fewer exacerbations. While the recommendations slightly differ based upon the age group, in those >12 years with mild persistent asthma, recommendations are for either daily ICS + as-needed short-acting beta-agonist (SABA), or as-needed ICS and SABA use. As in the Global Initiative for Asthma (GINA) guidelines, the panel also recommends single maintenance and rescue therapy (SMART) using ICS-formoterol inhalers for moderate to severe asthma. SMART has also been shown to reduce the risk of exacerbation. The clinician needs to use ICS-LABA medications where formoterol is the LABA component due to its quick onset of action (within 5 minutes, hence allowing it to be used as a rescue). Shared decision-making must be utilized when considering cost, insurance formulary restrictions, and perhaps delayed insurer and pharmacy adoption of these guidelines, as patients are likely to use more than one canister in a month when utilizing SMART.^3,4

LAMA is a pharmacologic class of long-acting inhaled bronchodilators. Guidelines addressed the role of LAMA in individuals aged 12 years and older. Three recommendations are made regarding the role of LAMA in this age group. In individuals with persistent, uncontrolled asthma while using ICS therapy, the guidelines recommend the addition of a LABA over LAMA therapy.⁵ LAMA can be added to ICS in individuals with uncontrolled asthma who cannot use LABA or are already on ICS-LABA maintenance therapy.

For those patients with mild to moderate allergic asthma, as defined by allergic sensitization via skin testing or in-vitro elevated serum IgE levels, the expert panel conditionally recommends subcutaneous immunotherapy (SCIT) as an adjunct treatment to standard pharmacotherapy. It is recommended only in those patients whose asthma remains controlled throughout initiation, build-up, and maintenance phases. SCIT should not be used for patients with severe asthma, and all attempts should be made to optimize asthma with standard therapy first. The risks and benefits of SCIT should be discussed with the specialist before starting therapy. Sublingual immunotherapy (SLIT) is not recommended for the treatment of asthma.

Regarding BT, the Expert Panel conditionally recommends against BT in individuals age 18 years and older with persistent asthma because of the small benefit to risk ratio and uncertain outcomes. Because there is a risk of worsening asthma control or inducing an exacerbation, it is advised that BT not be performed in individuals with an FEV <50%-60% or those with a history of life-threatening asthma. If BT is considered, it should be performed by an experienced specialist and should be done in conjunction with a clinical trial or registry to track its long-term safety and effectiveness.⁶ All efforts should be made to optimize asthma therapy and address comorbidities before pursuing BT.

This Expert Panel report provides a robust systematic review of the evidence that addresses key questions in the management of asthma. However, not providing any recommendations regarding the use of biologics was a significant gap. Further guidance regarding their role can be found in the GINA guidelines, and by the European Respiratory Society and American Thoracic Society, both of which were also published in 2020.^7,8Dr. Adrish is Clinical Assistant Professor, Bronx Care Health System, New York; Dr. Patil is Assistant Professor, Department of Respiratory Sleep and Critical Care Medicine, Maharashtra University of Health Sciences (MUHS), India; Dr. Oberle is Assistant Professor of Medicine, Associate Medical Director, Duke Asthma, Allergy and Airway Center, Durham, NC.
 

References

1. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. PMID: 33280709; PMCID: PMC7924476.

2. Zeiger RS, Schatz M, Zhang F, et al. Association of exhaled nitric oxide to asthma burden in asthmatics on inhaled corticosteroids. J Asthma. 2011;48:8-17.

3. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127-35.e8.

4. Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011;365:1990-2001.

5. Wechsler ME, Yawn BP, Fuhlbrigge AL, et al. Anticholinergic vs long-acting beta-agonist in combination with inhaled corticosteroids in black adults with asthma: The BELT randomized clinical trial. JAMA. 2015;314:1720-30.

6. Thomson NC, Rubin AS, Niven RM, et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med. 2011;11:8.

7. Global strategy for asthma management and prevention. 2020.

8. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55:1900588.

National Asthma Education and Prevention Program (NAEPP) published its last Expert Panel Report in 2007. Since that time, substantial progress has been made in understanding the pathophysiology and treatment of asthma. A new report has provided a much-needed update in the evaluation and management of asthma. It focuses on several priority topics jointly decided upon by the National Heart, Lung, and Blood Institute (NHLBI) Advisory Council Asthma Expert Working Group, the National Asthma Education and Prevention Program (NAEPP) participant organizations, and the public in 2015. These topics include the role of fractional exhaled nitric oxide (FeNO), allergen mitigation, intermittent inhaled corticosteroids (ICS), long-acting muscarinic agents (LAMA), immunotherapy, and bronchial thermoplasty (BT) in asthma management. This document did not include the subsequent new developments in the role of biologics in asthma. The following is a summary of the recommendations made in the 2020 Focused Updates to the Asthma Management Guidelines.¹

FeNO measurement is recommended to aid in asthma diagnosis and monitoring and to assist in ICS medication titration in individuals with asthma who are 5 years and older. The panel recommends that clinicians use FeNO levels, in conjunction with other relevant clinical data such as spirometry and asthma control questionnaires, for medical decision making. Similarly, when using FeNO to guide therapeutic changes in the ICS dose, the panel advises making changes based upon frequent measurements as a part of longitudinal assessment rather than one single measurement, as several factors can influence an FeNO measurement. Studies have demonstrated that a strategy that incorporates FeNO measurements into a treatment algorithm can reduce the risk of exacerbations; however, this has not been shown to reduce hospitalizations or quality of life.²

Allergen mitigation interventions, which can be used in individuals of all ages, are only recommended for those who have symptoms related to specific indoor aeroallergens exposure. This can be confirmed by skin testing or specific IgE in the appropriate clinical setting if specific allergen testing is not readily available. While most recommendations focus on using a multicomponent approach to allergen mitigation (ie, dust mite covers, HEPA filters, air purifiers, carpet removal, mold remediation, pest or pest removal, etc), pest removal was the only single-component approach that was deemed effective. Dust mite covers alone are unlikely to lead to significant improvement if not paired with additional mitigation strategies; however, note that there was low certainty about these recommendations. Ultimately, allergen mitigation should focus on addressing those identified triggers resulting in poor control of asthma. Simultaneously, the clinician should consider the resources and costs associated with some of these interventions.

The panel has recommended using ICS therapy for on-demand (prn) usage, even in those with mild persistent asthma, recognizing that earlier and more frequent on-demand ICS usage results in fewer exacerbations. While the recommendations slightly differ based upon the age group, in those >12 years with mild persistent asthma, recommendations are for either daily ICS + as-needed short-acting beta-agonist (SABA), or as-needed ICS and SABA use. As in the Global Initiative for Asthma (GINA) guidelines, the panel also recommends single maintenance and rescue therapy (SMART) using ICS-formoterol inhalers for moderate to severe asthma. SMART has also been shown to reduce the risk of exacerbation. The clinician needs to use ICS-LABA medications where formoterol is the LABA component due to its quick onset of action (within 5 minutes, hence allowing it to be used as a rescue). Shared decision-making must be utilized when considering cost, insurance formulary restrictions, and perhaps delayed insurer and pharmacy adoption of these guidelines, as patients are likely to use more than one canister in a month when utilizing SMART.^3,4

LAMA is a pharmacologic class of long-acting inhaled bronchodilators. Guidelines addressed the role of LAMA in individuals aged 12 years and older. Three recommendations are made regarding the role of LAMA in this age group. In individuals with persistent, uncontrolled asthma while using ICS therapy, the guidelines recommend the addition of a LABA over LAMA therapy.⁵ LAMA can be added to ICS in individuals with uncontrolled asthma who cannot use LABA or are already on ICS-LABA maintenance therapy.

For those patients with mild to moderate allergic asthma, as defined by allergic sensitization via skin testing or in-vitro elevated serum IgE levels, the expert panel conditionally recommends subcutaneous immunotherapy (SCIT) as an adjunct treatment to standard pharmacotherapy. It is recommended only in those patients whose asthma remains controlled throughout initiation, build-up, and maintenance phases. SCIT should not be used for patients with severe asthma, and all attempts should be made to optimize asthma with standard therapy first. The risks and benefits of SCIT should be discussed with the specialist before starting therapy. Sublingual immunotherapy (SLIT) is not recommended for the treatment of asthma.

Regarding BT, the Expert Panel conditionally recommends against BT in individuals age 18 years and older with persistent asthma because of the small benefit to risk ratio and uncertain outcomes. Because there is a risk of worsening asthma control or inducing an exacerbation, it is advised that BT not be performed in individuals with an FEV <50%-60% or those with a history of life-threatening asthma. If BT is considered, it should be performed by an experienced specialist and should be done in conjunction with a clinical trial or registry to track its long-term safety and effectiveness.⁶ All efforts should be made to optimize asthma therapy and address comorbidities before pursuing BT.

This Expert Panel report provides a robust systematic review of the evidence that addresses key questions in the management of asthma. However, not providing any recommendations regarding the use of biologics was a significant gap. Further guidance regarding their role can be found in the GINA guidelines, and by the European Respiratory Society and American Thoracic Society, both of which were also published in 2020.^7,8Dr. Adrish is Clinical Assistant Professor, Bronx Care Health System, New York; Dr. Patil is Assistant Professor, Department of Respiratory Sleep and Critical Care Medicine, Maharashtra University of Health Sciences (MUHS), India; Dr. Oberle is Assistant Professor of Medicine, Associate Medical Director, Duke Asthma, Allergy and Airway Center, Durham, NC.
 

References

1. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. PMID: 33280709; PMCID: PMC7924476.

2. Zeiger RS, Schatz M, Zhang F, et al. Association of exhaled nitric oxide to asthma burden in asthmatics on inhaled corticosteroids. J Asthma. 2011;48:8-17.

3. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127-35.e8.

4. Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011;365:1990-2001.

5. Wechsler ME, Yawn BP, Fuhlbrigge AL, et al. Anticholinergic vs long-acting beta-agonist in combination with inhaled corticosteroids in black adults with asthma: The BELT randomized clinical trial. JAMA. 2015;314:1720-30.

6. Thomson NC, Rubin AS, Niven RM, et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med. 2011;11:8.

7. Global strategy for asthma management and prevention. 2020.

8. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55:1900588.

National Asthma Education and Prevention Program (NAEPP) published its last Expert Panel Report in 2007. Since that time, substantial progress has been made in understanding the pathophysiology and treatment of asthma. A new report has provided a much-needed update in the evaluation and management of asthma. It focuses on several priority topics jointly decided upon by the National Heart, Lung, and Blood Institute (NHLBI) Advisory Council Asthma Expert Working Group, the National Asthma Education and Prevention Program (NAEPP) participant organizations, and the public in 2015. These topics include the role of fractional exhaled nitric oxide (FeNO), allergen mitigation, intermittent inhaled corticosteroids (ICS), long-acting muscarinic agents (LAMA), immunotherapy, and bronchial thermoplasty (BT) in asthma management. This document did not include the subsequent new developments in the role of biologics in asthma. The following is a summary of the recommendations made in the 2020 Focused Updates to the Asthma Management Guidelines.¹

FeNO measurement is recommended to aid in asthma diagnosis and monitoring and to assist in ICS medication titration in individuals with asthma who are 5 years and older. The panel recommends that clinicians use FeNO levels, in conjunction with other relevant clinical data such as spirometry and asthma control questionnaires, for medical decision making. Similarly, when using FeNO to guide therapeutic changes in the ICS dose, the panel advises making changes based upon frequent measurements as a part of longitudinal assessment rather than one single measurement, as several factors can influence an FeNO measurement. Studies have demonstrated that a strategy that incorporates FeNO measurements into a treatment algorithm can reduce the risk of exacerbations; however, this has not been shown to reduce hospitalizations or quality of life.²

Allergen mitigation interventions, which can be used in individuals of all ages, are only recommended for those who have symptoms related to specific indoor aeroallergens exposure. This can be confirmed by skin testing or specific IgE in the appropriate clinical setting if specific allergen testing is not readily available. While most recommendations focus on using a multicomponent approach to allergen mitigation (ie, dust mite covers, HEPA filters, air purifiers, carpet removal, mold remediation, pest or pest removal, etc), pest removal was the only single-component approach that was deemed effective. Dust mite covers alone are unlikely to lead to significant improvement if not paired with additional mitigation strategies; however, note that there was low certainty about these recommendations. Ultimately, allergen mitigation should focus on addressing those identified triggers resulting in poor control of asthma. Simultaneously, the clinician should consider the resources and costs associated with some of these interventions.

The panel has recommended using ICS therapy for on-demand (prn) usage, even in those with mild persistent asthma, recognizing that earlier and more frequent on-demand ICS usage results in fewer exacerbations. While the recommendations slightly differ based upon the age group, in those >12 years with mild persistent asthma, recommendations are for either daily ICS + as-needed short-acting beta-agonist (SABA), or as-needed ICS and SABA use. As in the Global Initiative for Asthma (GINA) guidelines, the panel also recommends single maintenance and rescue therapy (SMART) using ICS-formoterol inhalers for moderate to severe asthma. SMART has also been shown to reduce the risk of exacerbation. The clinician needs to use ICS-LABA medications where formoterol is the LABA component due to its quick onset of action (within 5 minutes, hence allowing it to be used as a rescue). Shared decision-making must be utilized when considering cost, insurance formulary restrictions, and perhaps delayed insurer and pharmacy adoption of these guidelines, as patients are likely to use more than one canister in a month when utilizing SMART.^3,4

LAMA is a pharmacologic class of long-acting inhaled bronchodilators. Guidelines addressed the role of LAMA in individuals aged 12 years and older. Three recommendations are made regarding the role of LAMA in this age group. In individuals with persistent, uncontrolled asthma while using ICS therapy, the guidelines recommend the addition of a LABA over LAMA therapy.⁵ LAMA can be added to ICS in individuals with uncontrolled asthma who cannot use LABA or are already on ICS-LABA maintenance therapy.

For those patients with mild to moderate allergic asthma, as defined by allergic sensitization via skin testing or in-vitro elevated serum IgE levels, the expert panel conditionally recommends subcutaneous immunotherapy (SCIT) as an adjunct treatment to standard pharmacotherapy. It is recommended only in those patients whose asthma remains controlled throughout initiation, build-up, and maintenance phases. SCIT should not be used for patients with severe asthma, and all attempts should be made to optimize asthma with standard therapy first. The risks and benefits of SCIT should be discussed with the specialist before starting therapy. Sublingual immunotherapy (SLIT) is not recommended for the treatment of asthma.

Regarding BT, the Expert Panel conditionally recommends against BT in individuals age 18 years and older with persistent asthma because of the small benefit to risk ratio and uncertain outcomes. Because there is a risk of worsening asthma control or inducing an exacerbation, it is advised that BT not be performed in individuals with an FEV <50%-60% or those with a history of life-threatening asthma. If BT is considered, it should be performed by an experienced specialist and should be done in conjunction with a clinical trial or registry to track its long-term safety and effectiveness.⁶ All efforts should be made to optimize asthma therapy and address comorbidities before pursuing BT.

This Expert Panel report provides a robust systematic review of the evidence that addresses key questions in the management of asthma. However, not providing any recommendations regarding the use of biologics was a significant gap. Further guidance regarding their role can be found in the GINA guidelines, and by the European Respiratory Society and American Thoracic Society, both of which were also published in 2020.^7,8Dr. Adrish is Clinical Assistant Professor, Bronx Care Health System, New York; Dr. Patil is Assistant Professor, Department of Respiratory Sleep and Critical Care Medicine, Maharashtra University of Health Sciences (MUHS), India; Dr. Oberle is Assistant Professor of Medicine, Associate Medical Director, Duke Asthma, Allergy and Airway Center, Durham, NC.
 

References

1. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. PMID: 33280709; PMCID: PMC7924476.

2. Zeiger RS, Schatz M, Zhang F, et al. Association of exhaled nitric oxide to asthma burden in asthmatics on inhaled corticosteroids. J Asthma. 2011;48:8-17.

3. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127-35.e8.

4. Zeiger RS, Mauger D, Bacharier LB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011;365:1990-2001.

5. Wechsler ME, Yawn BP, Fuhlbrigge AL, et al. Anticholinergic vs long-acting beta-agonist in combination with inhaled corticosteroids in black adults with asthma: The BELT randomized clinical trial. JAMA. 2015;314:1720-30.

6. Thomson NC, Rubin AS, Niven RM, et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med. 2011;11:8.

7. Global strategy for asthma management and prevention. 2020.

8. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55:1900588.

With the confidence that comes from 25 years of strong guidance and inspired leadership, the CHEST Foundation is ready to step into a new role as conversation starters, access granters, and change makers. The Foundation will spend this anniversary year celebrating the past and sharing the bold future ahead with our community.

Leaders of the past

Founded on the promise of delivering grants and branching into education and outreach, the Foundation’s accomplishments are endless:

• Creating engaging tobacco cessation and educational programming.
• Launching the “Beyond Our Walls” campaign to support CHEST’s Simulation Center.
• Partnering with the Popovich family to secure a substantial ILD endowment.
• Providing COVID-19 microgrants aimed at community outreach.
• Launching a Listening Tours campaign to address health disparities.
• Producing a complimentary oxygen toolkit for patients across the United States.

Trailblazers of the future

The CHEST Foundation is rising to a new level of philanthropic work by – creating premier patient education tools, aggressively tackling health disparities in marginalized communities, awarding millions in community grants, and partnering with physicians to offer better resources to patients.

While we remember the journey here, it’s now time to blaze into the future. We hope you’ll join us by learning more about our anniversary, attending our virtual events, and getting involved with the Foundation.

Visit chestfoundation.org/25th-anniversary to learn more.



Title: Share Our Story on Social Media

Paragraph: Follow the hashtag #CHESTFoundation25 on Twitter, Instagram, and Facebook. We’ll be asking questions every month and would love to hear from you!


 

With the confidence that comes from 25 years of strong guidance and inspired leadership, the CHEST Foundation is ready to step into a new role as conversation starters, access granters, and change makers. The Foundation will spend this anniversary year celebrating the past and sharing the bold future ahead with our community.

Leaders of the past

Founded on the promise of delivering grants and branching into education and outreach, the Foundation’s accomplishments are endless:

• Creating engaging tobacco cessation and educational programming.
• Launching the “Beyond Our Walls” campaign to support CHEST’s Simulation Center.
• Partnering with the Popovich family to secure a substantial ILD endowment.
• Providing COVID-19 microgrants aimed at community outreach.
• Launching a Listening Tours campaign to address health disparities.
• Producing a complimentary oxygen toolkit for patients across the United States.

Trailblazers of the future

The CHEST Foundation is rising to a new level of philanthropic work by – creating premier patient education tools, aggressively tackling health disparities in marginalized communities, awarding millions in community grants, and partnering with physicians to offer better resources to patients.

While we remember the journey here, it’s now time to blaze into the future. We hope you’ll join us by learning more about our anniversary, attending our virtual events, and getting involved with the Foundation.

Visit chestfoundation.org/25th-anniversary to learn more.



Title: Share Our Story on Social Media

Paragraph: Follow the hashtag #CHESTFoundation25 on Twitter, Instagram, and Facebook. We’ll be asking questions every month and would love to hear from you!


 

With the confidence that comes from 25 years of strong guidance and inspired leadership, the CHEST Foundation is ready to step into a new role as conversation starters, access granters, and change makers. The Foundation will spend this anniversary year celebrating the past and sharing the bold future ahead with our community.

Leaders of the past

Founded on the promise of delivering grants and branching into education and outreach, the Foundation’s accomplishments are endless:

• Creating engaging tobacco cessation and educational programming.
• Launching the “Beyond Our Walls” campaign to support CHEST’s Simulation Center.
• Partnering with the Popovich family to secure a substantial ILD endowment.
• Providing COVID-19 microgrants aimed at community outreach.
• Launching a Listening Tours campaign to address health disparities.
• Producing a complimentary oxygen toolkit for patients across the United States.

Trailblazers of the future

The CHEST Foundation is rising to a new level of philanthropic work by – creating premier patient education tools, aggressively tackling health disparities in marginalized communities, awarding millions in community grants, and partnering with physicians to offer better resources to patients.

While we remember the journey here, it’s now time to blaze into the future. We hope you’ll join us by learning more about our anniversary, attending our virtual events, and getting involved with the Foundation.

Visit chestfoundation.org/25th-anniversary to learn more.



Title: Share Our Story on Social Media

Paragraph: Follow the hashtag #CHESTFoundation25 on Twitter, Instagram, and Facebook. We’ll be asking questions every month and would love to hear from you!


 

Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.

Courtesy Orange County Convention Center

For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.

Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
 

Conference center and hotels

CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.

Visiting local attractions

You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.

When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.

Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.

And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.

Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.

Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.

Courtesy Orange County Convention Center

For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.

Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
 

Conference center and hotels

CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.

Visiting local attractions

You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.

When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.

Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.

And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.

Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.

Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.

Courtesy Orange County Convention Center

For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.

Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
 

Conference center and hotels

CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.

Visiting local attractions

You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.

When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.

Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.

And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.

Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.

Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.

The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
 

The Johns Hopkins experience

Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.

Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.

Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.

Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.

Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.

The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.

Overall, clinically relevant findings were:

• Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
• Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
• Some patients improved clinically after IVIg therapy, but mortality was high overall.
• Infliximab therapy, alone or in combination with IVIg, was ineffective.

The Memorial Sloan Kettering experience

Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.

Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.

Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.

The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).

A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.

Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.

The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.

In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.

Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.

Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.

Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.

Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.

Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.

The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
 

Lessons for clinicians

The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.

Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.

This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.

The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.

Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.

Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.

Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.

Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.

Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.

The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.

The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.

The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
 

The Johns Hopkins experience

Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.

Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.

Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.

Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.

Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.

The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.

Overall, clinically relevant findings were:

• Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
• Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
• Some patients improved clinically after IVIg therapy, but mortality was high overall.
• Infliximab therapy, alone or in combination with IVIg, was ineffective.

The Memorial Sloan Kettering experience

Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.

Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.

Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.

The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).

A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.

Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.

The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.

In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.

Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.

Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.

Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.

Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.

Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.

The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
 

Lessons for clinicians

The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.

Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.

This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.

The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.

Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.

Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.

Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.

Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.

Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.

The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.

The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.

The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
 

The Johns Hopkins experience

Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.

Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.

Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.

Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.

Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.

The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.

Overall, clinically relevant findings were:

• Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
• Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
• Some patients improved clinically after IVIg therapy, but mortality was high overall.
• Infliximab therapy, alone or in combination with IVIg, was ineffective.

The Memorial Sloan Kettering experience

Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.

Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.

Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.

The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).

A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.

Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.

The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.

In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.

Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.

Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.

Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.

Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.

Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.

The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
 

Lessons for clinicians

The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.

Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.

This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.

The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.

Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.

Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.

Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.

Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.

Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.

The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.

The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.

Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.

“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.

She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).

In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.

“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.

A similar picture has emerged elsewhere.

In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.

In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).

Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.

The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.

There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.

“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.

In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.

By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.

Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.

After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.

The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.

The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.

His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.

In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.

Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.

Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.

“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”

He suspects that there is more at play than screening cancellations.

In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.

“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.

She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.

Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.

Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.

“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.

Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.

Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.

“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”

In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.

Public health initiatives to rebalance the messaging are now underway.

Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”

In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”

“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”

Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.

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

Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.

Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.

“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.

She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).

In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.

“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.

A similar picture has emerged elsewhere.

In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.

In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).

Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.

The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.

There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.

“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.

In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.

By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.

Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.

After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.

The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.

The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.

His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.

In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.

Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.

Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.

“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”

He suspects that there is more at play than screening cancellations.

In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.

“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.

She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.

Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.

Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.

“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.

Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.

Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.

“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”

In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.

Public health initiatives to rebalance the messaging are now underway.

Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”

In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”

“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”

Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.

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

Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.

Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.

“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.

She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).

In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.

“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.

A similar picture has emerged elsewhere.

In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.

In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).

Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.

The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.

There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.

“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.

In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.

By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.

Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.

After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.

The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.

The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.

His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.

In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.

Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.

Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.

“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”

He suspects that there is more at play than screening cancellations.

In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.

“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.

She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.

Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.

Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.

“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.

Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.

Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.

“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”

In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.

Public health initiatives to rebalance the messaging are now underway.

Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”

In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”

“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”

Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.

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

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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