Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Giants in Chest Medicine

Emeritus Professor Peter D. Wagner, MD

By Dr. Tatum S. Simonson



State of the Journal Editorial

Spread the Word About CHEST in 2019: Innovations, Introductions,

and Farewells. By Dr. R. S. Irwin, et al.



Original Research

Meta-analysis of Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis. By Dr. D. Bedard, et al.



Surgical Disparities Among Patients With Stage I Lung Cancer in the National Lung

Screening Trial. By Dr. A. A. Balekian, et al.



Evidence-Based Medicine

Clinically Diagnosing Pertussis-Associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report. By Dr. A. Moore, et al.



Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza: CHEST Guideline and Expert Panel Report. By Dr. A. T. Hill, et al.

Giants in Chest Medicine

Emeritus Professor Peter D. Wagner, MD

By Dr. Tatum S. Simonson



State of the Journal Editorial

Spread the Word About CHEST in 2019: Innovations, Introductions,

and Farewells. By Dr. R. S. Irwin, et al.



Original Research

Meta-analysis of Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis. By Dr. D. Bedard, et al.



Surgical Disparities Among Patients With Stage I Lung Cancer in the National Lung

Screening Trial. By Dr. A. A. Balekian, et al.



Evidence-Based Medicine

Clinically Diagnosing Pertussis-Associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report. By Dr. A. Moore, et al.



Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza: CHEST Guideline and Expert Panel Report. By Dr. A. T. Hill, et al.

Giants in Chest Medicine

Emeritus Professor Peter D. Wagner, MD

By Dr. Tatum S. Simonson



State of the Journal Editorial

Spread the Word About CHEST in 2019: Innovations, Introductions,

and Farewells. By Dr. R. S. Irwin, et al.



Original Research

Meta-analysis of Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis. By Dr. D. Bedard, et al.



Surgical Disparities Among Patients With Stage I Lung Cancer in the National Lung

Screening Trial. By Dr. A. A. Balekian, et al.



Evidence-Based Medicine

Clinically Diagnosing Pertussis-Associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report. By Dr. A. Moore, et al.



Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza: CHEST Guideline and Expert Panel Report. By Dr. A. T. Hill, et al.

The wisdom of the crowd is the collective opinion of a group of individuals rather than that of a single expert. At CHEST, the makeup of our membership is diverse and energetic, and it comprises individuals with unique expertise who not only serve as faculty but who are also eager for opportunities themselves to learn. That collective wisdom, leveraged over the entire membership, is what the leadership of CHEST will be listening to this year as we create new educational products and continuously improve the annual meeting and other courses held throughout the year. From broad-based general overviews such as CHEST’s board reviews, to more specific courses such as training in bedside ultrasound or ventilator management, each are geared to make all of us better clinicians who will recognize and provide the latest and most effective treatments for our patients. If you had the opportunity to attend my opening address at the CHEST annual meeting in San Antonio in October, you heard me talk about the innate wisdom of “the crowd.” We all have various “crowds” in our lives -- our work colleagues, families, and relationships in professional societies. I reminded the audience that if we take the time to listen to each of these “crowds,” they usually know the answers. In the coming year, we, as a leadership team for CHEST, will be focusing on being better listeners and utilizing “our crowd” of members to better connect in order to develop educational products that will train clinicians, educators, and researchers in the very latest and most effective care in pulmonary, critical care, and sleep medicine.

•Digital Strategy Task Force – This multidisciplinary group, composed of both volunteer members and association staff, has been assigned to evaluate the user experience associated with existing CHEST content delivery platforms and highlight opportunities for improvements. In this effort, they will identify trends that will enable the organization to better execute on the digital-dependent strategies in the organization’s strategic plan in a successful way. The group will be making recommendations to the Board of Regents that will include timelines, goals, and specific objectives, define organizational voice and brand messaging present on web and other platforms, and create specific metrics to measure the user experience on an ongoing basis.

•Optimizing Board Review Courses – CHEST will be looking at ways to present some content on digital platforms that are difficult to teach in a classic didactic format. Topics such as acid-base disturbances and biostatistics are more effectively presented using a digital, problem-based format. Efforts will be made to shorten board review courses slightly without compromising quality or jeopardizing coverage of content and to incorporate succinct bulleted summaries of each topic covered. In addition, plans are in place to create new courses that will train learners the techniques for passing the new “low stakes” board examination offered by the ABIM.

•Making membership more affordable for international colleagues – New discounted membership rates have been launched to allow international members to obtain the “Enhanced” level of membership to be eligible for fellowship in the association (ie, the FCCP designation). Volume discounts have been introduced for regional chapters and organizations to allow health-care team members from around the world to join CHEST in conjunction with their local society at a fraction of the cost of a single member rate.

•Patient education modules from the CHEST Foundation – A variety of patient education modules are now available to providers, as well as to the general public for information on a wide array of topics – from correct use of inhalers to state-of-the-art therapies for COPD or lung cancer.

Improved opportunities for member participation -- From improved instructions for joining a CHEST NetWork to specific orientation instructions for new members of the Board of Regents, improved communications have become available to help members become better acquainted with the framework of the organization and allow them to become more effective once they begin new leadership roles.

•Embracing innovation -- This year, the organization will launch CHEST Inspiration, a program that involves development of an environmental scan to be shared with our members regarding how CHEST can be a differentiator in an environment where quality education is becoming more accessible and, as a result, more competitive. As part of this initiative, CHEST will plan to host a series of focus group sessions to act on the environmental scan and will also roll out an innovation competition at the 2019 annual meeting in New Orleans in October.

•Expanded international strategy – CHEST is responding to the requests from member groups in countries within Asia, Europe, Latin America, and the Middle East to hold a CHEST Congress each spring to bring the best of the CHEST annual meeting to our colleagues from around the world who may not be able to travel to the meeting held in the U.S., as well as a more intimate board review-like meeting each summer in various regions of the world. For example, this year, the College will host a CHEST Congress in Bangkok, Thailand, April 10-12, and a regional meeting in Athens, Greece, June 27-29.

We are committed to improving communication with our members and encouraging innovation regardless of their prior participation levels. CHEST will continue to bring its brand of education focused on more hands-on learning and team-based knowledge using simulation, serious gaming, and artificial intelligence in the years ahead. CHEST leaders have begun to be active on social media, and we will be introducing new platforms for all members to better understand what is happening from a leadership perspective. Together, we will be able to harness the collective wisdom of our talented and innovative members in order to make a lasting difference for our patients.

The wisdom of the crowd is the collective opinion of a group of individuals rather than that of a single expert. At CHEST, the makeup of our membership is diverse and energetic, and it comprises individuals with unique expertise who not only serve as faculty but who are also eager for opportunities themselves to learn. That collective wisdom, leveraged over the entire membership, is what the leadership of CHEST will be listening to this year as we create new educational products and continuously improve the annual meeting and other courses held throughout the year. From broad-based general overviews such as CHEST’s board reviews, to more specific courses such as training in bedside ultrasound or ventilator management, each are geared to make all of us better clinicians who will recognize and provide the latest and most effective treatments for our patients. If you had the opportunity to attend my opening address at the CHEST annual meeting in San Antonio in October, you heard me talk about the innate wisdom of “the crowd.” We all have various “crowds” in our lives -- our work colleagues, families, and relationships in professional societies. I reminded the audience that if we take the time to listen to each of these “crowds,” they usually know the answers. In the coming year, we, as a leadership team for CHEST, will be focusing on being better listeners and utilizing “our crowd” of members to better connect in order to develop educational products that will train clinicians, educators, and researchers in the very latest and most effective care in pulmonary, critical care, and sleep medicine.

•Digital Strategy Task Force – This multidisciplinary group, composed of both volunteer members and association staff, has been assigned to evaluate the user experience associated with existing CHEST content delivery platforms and highlight opportunities for improvements. In this effort, they will identify trends that will enable the organization to better execute on the digital-dependent strategies in the organization’s strategic plan in a successful way. The group will be making recommendations to the Board of Regents that will include timelines, goals, and specific objectives, define organizational voice and brand messaging present on web and other platforms, and create specific metrics to measure the user experience on an ongoing basis.

•Optimizing Board Review Courses – CHEST will be looking at ways to present some content on digital platforms that are difficult to teach in a classic didactic format. Topics such as acid-base disturbances and biostatistics are more effectively presented using a digital, problem-based format. Efforts will be made to shorten board review courses slightly without compromising quality or jeopardizing coverage of content and to incorporate succinct bulleted summaries of each topic covered. In addition, plans are in place to create new courses that will train learners the techniques for passing the new “low stakes” board examination offered by the ABIM.

•Making membership more affordable for international colleagues – New discounted membership rates have been launched to allow international members to obtain the “Enhanced” level of membership to be eligible for fellowship in the association (ie, the FCCP designation). Volume discounts have been introduced for regional chapters and organizations to allow health-care team members from around the world to join CHEST in conjunction with their local society at a fraction of the cost of a single member rate.

•Patient education modules from the CHEST Foundation – A variety of patient education modules are now available to providers, as well as to the general public for information on a wide array of topics – from correct use of inhalers to state-of-the-art therapies for COPD or lung cancer.

Improved opportunities for member participation -- From improved instructions for joining a CHEST NetWork to specific orientation instructions for new members of the Board of Regents, improved communications have become available to help members become better acquainted with the framework of the organization and allow them to become more effective once they begin new leadership roles.

•Embracing innovation -- This year, the organization will launch CHEST Inspiration, a program that involves development of an environmental scan to be shared with our members regarding how CHEST can be a differentiator in an environment where quality education is becoming more accessible and, as a result, more competitive. As part of this initiative, CHEST will plan to host a series of focus group sessions to act on the environmental scan and will also roll out an innovation competition at the 2019 annual meeting in New Orleans in October.

•Expanded international strategy – CHEST is responding to the requests from member groups in countries within Asia, Europe, Latin America, and the Middle East to hold a CHEST Congress each spring to bring the best of the CHEST annual meeting to our colleagues from around the world who may not be able to travel to the meeting held in the U.S., as well as a more intimate board review-like meeting each summer in various regions of the world. For example, this year, the College will host a CHEST Congress in Bangkok, Thailand, April 10-12, and a regional meeting in Athens, Greece, June 27-29.

We are committed to improving communication with our members and encouraging innovation regardless of their prior participation levels. CHEST will continue to bring its brand of education focused on more hands-on learning and team-based knowledge using simulation, serious gaming, and artificial intelligence in the years ahead. CHEST leaders have begun to be active on social media, and we will be introducing new platforms for all members to better understand what is happening from a leadership perspective. Together, we will be able to harness the collective wisdom of our talented and innovative members in order to make a lasting difference for our patients.

The wisdom of the crowd is the collective opinion of a group of individuals rather than that of a single expert. At CHEST, the makeup of our membership is diverse and energetic, and it comprises individuals with unique expertise who not only serve as faculty but who are also eager for opportunities themselves to learn. That collective wisdom, leveraged over the entire membership, is what the leadership of CHEST will be listening to this year as we create new educational products and continuously improve the annual meeting and other courses held throughout the year. From broad-based general overviews such as CHEST’s board reviews, to more specific courses such as training in bedside ultrasound or ventilator management, each are geared to make all of us better clinicians who will recognize and provide the latest and most effective treatments for our patients. If you had the opportunity to attend my opening address at the CHEST annual meeting in San Antonio in October, you heard me talk about the innate wisdom of “the crowd.” We all have various “crowds” in our lives -- our work colleagues, families, and relationships in professional societies. I reminded the audience that if we take the time to listen to each of these “crowds,” they usually know the answers. In the coming year, we, as a leadership team for CHEST, will be focusing on being better listeners and utilizing “our crowd” of members to better connect in order to develop educational products that will train clinicians, educators, and researchers in the very latest and most effective care in pulmonary, critical care, and sleep medicine.

•Digital Strategy Task Force – This multidisciplinary group, composed of both volunteer members and association staff, has been assigned to evaluate the user experience associated with existing CHEST content delivery platforms and highlight opportunities for improvements. In this effort, they will identify trends that will enable the organization to better execute on the digital-dependent strategies in the organization’s strategic plan in a successful way. The group will be making recommendations to the Board of Regents that will include timelines, goals, and specific objectives, define organizational voice and brand messaging present on web and other platforms, and create specific metrics to measure the user experience on an ongoing basis.

•Optimizing Board Review Courses – CHEST will be looking at ways to present some content on digital platforms that are difficult to teach in a classic didactic format. Topics such as acid-base disturbances and biostatistics are more effectively presented using a digital, problem-based format. Efforts will be made to shorten board review courses slightly without compromising quality or jeopardizing coverage of content and to incorporate succinct bulleted summaries of each topic covered. In addition, plans are in place to create new courses that will train learners the techniques for passing the new “low stakes” board examination offered by the ABIM.

•Making membership more affordable for international colleagues – New discounted membership rates have been launched to allow international members to obtain the “Enhanced” level of membership to be eligible for fellowship in the association (ie, the FCCP designation). Volume discounts have been introduced for regional chapters and organizations to allow health-care team members from around the world to join CHEST in conjunction with their local society at a fraction of the cost of a single member rate.

•Patient education modules from the CHEST Foundation – A variety of patient education modules are now available to providers, as well as to the general public for information on a wide array of topics – from correct use of inhalers to state-of-the-art therapies for COPD or lung cancer.

Improved opportunities for member participation -- From improved instructions for joining a CHEST NetWork to specific orientation instructions for new members of the Board of Regents, improved communications have become available to help members become better acquainted with the framework of the organization and allow them to become more effective once they begin new leadership roles.

•Embracing innovation -- This year, the organization will launch CHEST Inspiration, a program that involves development of an environmental scan to be shared with our members regarding how CHEST can be a differentiator in an environment where quality education is becoming more accessible and, as a result, more competitive. As part of this initiative, CHEST will plan to host a series of focus group sessions to act on the environmental scan and will also roll out an innovation competition at the 2019 annual meeting in New Orleans in October.

•Expanded international strategy – CHEST is responding to the requests from member groups in countries within Asia, Europe, Latin America, and the Middle East to hold a CHEST Congress each spring to bring the best of the CHEST annual meeting to our colleagues from around the world who may not be able to travel to the meeting held in the U.S., as well as a more intimate board review-like meeting each summer in various regions of the world. For example, this year, the College will host a CHEST Congress in Bangkok, Thailand, April 10-12, and a regional meeting in Athens, Greece, June 27-29.

We are committed to improving communication with our members and encouraging innovation regardless of their prior participation levels. CHEST will continue to bring its brand of education focused on more hands-on learning and team-based knowledge using simulation, serious gaming, and artificial intelligence in the years ahead. CHEST leaders have begun to be active on social media, and we will be introducing new platforms for all members to better understand what is happening from a leadership perspective. Together, we will be able to harness the collective wisdom of our talented and innovative members in order to make a lasting difference for our patients.

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

More than 5 million Americans are living with Alzheimer disease (AD), making this the leading cause of dementia in the United States. This number is projected to nearly triple to 14 million people by 2060 (Matthews KA, et al. Alzheimers Dement. 2018 Sep 17. doi: 10.1016/j.jalz.2018.06.3063. [Epub ahead of print]).

As the dementia progresses, sleep also tends to worsen. Currently, clinicians improve sleep in patients already diagnosed with AD through diagnosis and treatment of sleep disorders, such as insomnia and sleep apnea to improve overall functioning and quality of life. Treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients diagnosed with AD has shown to improve cognition and other neurocognitive measures (Ancoli-Israel S, et al. J Am Geriatr Soc. 2008;56[11]:2076).

However, there is mounting interest in evaluating how poor sleep could lead to future development of AD or serve as a marker for AD disease in preclinical or asymptomatic populations. Sleep symptoms can be a precursor of other neurological diseases; for example, dream enactment (REM sleep behavior disorder) can precede onset of neurodegenerative disease (Parkinson disease) by decades. Increasing evidence suggests that sleep disruption seen in early or even preclinical AD contributes to its onset and progression. In response to this growing body of research, in June 2018, the American Academy of Sleep Medicine (AASM) issued a health advisory to patients and providers to consider early intervention to ensure sufficient sleep and to treat sleep disorders to assist prevention or delaying onset of AD.
 

Poor Sleep as a Risk Factor for Alzheimer Disease

Epidemiologic studies (both cross-sectional and prospective studies) have demonstrated that fragmented sleep in cognitively normal individuals is a risk factor for the future development of symptomatic AD (Bubu OM, et al. Sleep. 2017[Jan]:1;40). The pathogenesis of AD includes abnormal accumulation of the protein, amyloid-β (Aβ), in the brain as insoluble extracellular plaques followed by intracellular aggregation of tau, neuronal loss, and cognitive dysfunction. Aβ deposition in the brain begins approximately15 to 20 years before the onset of cognitive impairment and serves as an early biomarker of AD. Accumulation of Aβ results from imbalance between production and clearance of the protein from the central nervous system.

Numerous studies have demonstrated that people with disrupted sleep may show early evidence of AD disease, such as Aβ deposition compared with healthy sleepers. In one study, cognitively normal people with Aβ plaque disease had worse sleep efficiency and increased nap frequency measured by actigraphy as compared with cognitively normal individuals without Aβ plaques (Ju YE, et al. JAMA Neurol. 2013 [May];70[5]:587). Further, a recent study found that self-reported daytime sleepiness was associated with longitudinal increases in Aβ deposition (Carvalho DZ, et al. JAMA Neurol. 2018[Jun];75[6]:672).
 

Possible Mechanisms

Possible mechanisms have been suggested to explain how poor sleep may lead to AD. Over the past 10 years, sleep deprivation was found to increase Aβ concentrations in both a mouse model (Kang JE, et al. Science. 2009; 326:1005) and humans, most likely through increased production and/or release of Aβ (Lucey BP, et al. Ann Neurol. 2018; 83[1]:197). Sleep also appears to increase clearance of proteins and other molecules via bulk fluid flow (“glymphatic” clearance). Glymphatic clearance may enable the removal of interstitial toxic proteins, such as Aβ, through a dynamic interaction between the cerebrospinal fluid and the interstitial fluid, where astrocytes facilitate extracellular fluid transit though the brain during sleep (Xie L, et al. Science. 2013;342:373). Since Aβ deposition in the brain is concentration-dependent, higher Aβ levels from sleep disturbance could lead to greater deposition in the brain.
 

Circadian Rhythm and Alzheimer Disease

Another mechanism linking sleep to the pathogenesis of AD includes disruption of the circadian rhythm, which is commonly seen in patients with AD. Studies have linked populations who suffer from circadian rhythm disorders to higher rates of dementia (Tranah GJ, et al. Ann Neurol. 2011;70[5]:722). Circadian disruption may predispose the brain to neurodegenerative conditions by altering immune function, disrupting endocrine function, increasing inflammation and oxidative stress, or affecting neurogenesis (in specific areas such as the hippocampus). Thus, inadequate sleep could prime the brain for neurodegeneration by multiple pathways.
 

Obstructive Sleep Apnea and Alzheimer’s Disease

Sleep disruption and chronic intermittent hypoxia secondary to untreated OSA has also been associated with AD. Numerous studies have shown that sleep-disordered breathing is associated with AD risk and that AD patients have higher rates of OSA. For instance, a study in older women found that moderate and severe sleep-disordered breathing was associated with an increased risk of future cognitive impairment and dementia (Yaffe K, et al. JAMA. 2011[Aug]:10;306[6]:613). In addition to sleep disruption from sleep apnea affecting Aβ as detailed above, hypoxia from sleep apnea may also alter risk of future AD.
 

Future Directions

Studies support a clear bidirectional relationship between AD and sleep. As researchers continue to investigate sleep as a marker for AD, others are exploring the implications of using sleep interventions to prevent and/or delay the onset of AD. Patients with poor and disrupted sleep may be the ideal candidates for sleep interventions to lower the risk of AD, such as treating OSA with CPAP therapy or insomnia with hypnotic medication or cognitive behavioral therapy. These therapies are already well-studied and approved for human use, allowing for rapid translation to future intervention trials.



Dr. Malhotra is Associate Professor, Sleep Medicine Section; and Dr. Lucey is Assistant Professor, Director-Sleep Medicine Section; Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
 

While in San Antonio for CHEST 2018, CHEST Foundation caught up with the recipient of our 2017 CHEST Foundation Research Grant in Asthma, Drew Harris, MD, to learn about the impact of winning a CHEST Foundation Research grant had on his community and career. Dr. Harris’ project created a medical-legal partnership to target many of the social determinants of asthma and help address them beyond the typical scope a provider can offer in a traditional visit.

“Currently, we have a full-time lawyer, two social workers, and people in Public Health Sciences program as well as law students at The University of Virginia (UVA) all working together to address the needs of the community,” Harris stated. “Public health students conduct asthma screenings in any of the four clinics we partner with within the UVA system and bring their findings to the larger group. From there, we figure out how to best intervene for these people and connect them with our lawyer if there are housing or workplace discrimination concerns.”

Dr. Harris recently received NIH funding for his approach and has since expanded this medical-legal partnership at the University of Virginia. “The grant I received last year from the CHEST Foundation funded a pilot version of my project that I then was able to share with a larger audience and ultimately secure federal funding for,” Dr. Harris shared.

“The NIH grant was awarded through the lens of implementation science. We know what works in asthma medication and environmental and social factors that help improve patients’ lives. But we do a poor job on actually DOING it. Our project addresses barriers to fixing these social needs and brings a team together to help fix these other problems that are hard for just a medical provider to address.” Dr. Harris continued, “Social needs and determinants of health are starting to receive more attention in pulmonary medicine, so we are really hitting the ground at the right time. Everyone understands that these are important determinants of health, but they lack the tools to help improve patients’ lives. We are creating those.”

Your donations support clinical research projects like this grant for Dr.Harris. Please consider making a donation to support next year’s grants. https://foundation.chestnet.org/donate/

“A middle-aged textile worker who entered Charlottesville as a Syrian refugee several years ago had been unable to work much in Charlottesville due to work-related asthma. She was denied disability due to insufficient work time. Without a network of friends or family to turn to, this family was struggling in poverty with housing and food insecurity. By connecting with this CHEST Foundation-supported program, this patient received needed advocacy and support of doctors, social workers, and legal aid attorneys. She is now supported in an application for a monthly subsidy to help her immediate social needs while we work towards a more permanent solution. Our program has also helped patients with health-harming social needs, including lack of access to care (by helping patients apply for and enroll in Medicaid, for example), housing issues (such as mold and unresponsive landlords), and intimate partner violence. Working together as a team, we are able to provide advocacy to improve the health and well-being of our vulnerable community members. This program addresses issues that are important to my community. Without the hard work and dedication of my colleagues, the community at large, and all those committed to confronting these problems, many families would not get what they need to thrive. I am proud and feel lucky to dedicate my time to support my patients and my community. Thank you to the CHEST Foundation and all those who support it to ensure that ALL patients receive the care they deserve.”

—Drew Harris, MD

While in San Antonio for CHEST 2018, CHEST Foundation caught up with the recipient of our 2017 CHEST Foundation Research Grant in Asthma, Drew Harris, MD, to learn about the impact of winning a CHEST Foundation Research grant had on his community and career. Dr. Harris’ project created a medical-legal partnership to target many of the social determinants of asthma and help address them beyond the typical scope a provider can offer in a traditional visit.

“Currently, we have a full-time lawyer, two social workers, and people in Public Health Sciences program as well as law students at The University of Virginia (UVA) all working together to address the needs of the community,” Harris stated. “Public health students conduct asthma screenings in any of the four clinics we partner with within the UVA system and bring their findings to the larger group. From there, we figure out how to best intervene for these people and connect them with our lawyer if there are housing or workplace discrimination concerns.”

Dr. Harris recently received NIH funding for his approach and has since expanded this medical-legal partnership at the University of Virginia. “The grant I received last year from the CHEST Foundation funded a pilot version of my project that I then was able to share with a larger audience and ultimately secure federal funding for,” Dr. Harris shared.

“The NIH grant was awarded through the lens of implementation science. We know what works in asthma medication and environmental and social factors that help improve patients’ lives. But we do a poor job on actually DOING it. Our project addresses barriers to fixing these social needs and brings a team together to help fix these other problems that are hard for just a medical provider to address.” Dr. Harris continued, “Social needs and determinants of health are starting to receive more attention in pulmonary medicine, so we are really hitting the ground at the right time. Everyone understands that these are important determinants of health, but they lack the tools to help improve patients’ lives. We are creating those.”

Your donations support clinical research projects like this grant for Dr.Harris. Please consider making a donation to support next year’s grants. https://foundation.chestnet.org/donate/

“A middle-aged textile worker who entered Charlottesville as a Syrian refugee several years ago had been unable to work much in Charlottesville due to work-related asthma. She was denied disability due to insufficient work time. Without a network of friends or family to turn to, this family was struggling in poverty with housing and food insecurity. By connecting with this CHEST Foundation-supported program, this patient received needed advocacy and support of doctors, social workers, and legal aid attorneys. She is now supported in an application for a monthly subsidy to help her immediate social needs while we work towards a more permanent solution. Our program has also helped patients with health-harming social needs, including lack of access to care (by helping patients apply for and enroll in Medicaid, for example), housing issues (such as mold and unresponsive landlords), and intimate partner violence. Working together as a team, we are able to provide advocacy to improve the health and well-being of our vulnerable community members. This program addresses issues that are important to my community. Without the hard work and dedication of my colleagues, the community at large, and all those committed to confronting these problems, many families would not get what they need to thrive. I am proud and feel lucky to dedicate my time to support my patients and my community. Thank you to the CHEST Foundation and all those who support it to ensure that ALL patients receive the care they deserve.”

—Drew Harris, MD

While in San Antonio for CHEST 2018, CHEST Foundation caught up with the recipient of our 2017 CHEST Foundation Research Grant in Asthma, Drew Harris, MD, to learn about the impact of winning a CHEST Foundation Research grant had on his community and career. Dr. Harris’ project created a medical-legal partnership to target many of the social determinants of asthma and help address them beyond the typical scope a provider can offer in a traditional visit.

“Currently, we have a full-time lawyer, two social workers, and people in Public Health Sciences program as well as law students at The University of Virginia (UVA) all working together to address the needs of the community,” Harris stated. “Public health students conduct asthma screenings in any of the four clinics we partner with within the UVA system and bring their findings to the larger group. From there, we figure out how to best intervene for these people and connect them with our lawyer if there are housing or workplace discrimination concerns.”

Dr. Harris recently received NIH funding for his approach and has since expanded this medical-legal partnership at the University of Virginia. “The grant I received last year from the CHEST Foundation funded a pilot version of my project that I then was able to share with a larger audience and ultimately secure federal funding for,” Dr. Harris shared.

“The NIH grant was awarded through the lens of implementation science. We know what works in asthma medication and environmental and social factors that help improve patients’ lives. But we do a poor job on actually DOING it. Our project addresses barriers to fixing these social needs and brings a team together to help fix these other problems that are hard for just a medical provider to address.” Dr. Harris continued, “Social needs and determinants of health are starting to receive more attention in pulmonary medicine, so we are really hitting the ground at the right time. Everyone understands that these are important determinants of health, but they lack the tools to help improve patients’ lives. We are creating those.”

Your donations support clinical research projects like this grant for Dr.Harris. Please consider making a donation to support next year’s grants. https://foundation.chestnet.org/donate/

“A middle-aged textile worker who entered Charlottesville as a Syrian refugee several years ago had been unable to work much in Charlottesville due to work-related asthma. She was denied disability due to insufficient work time. Without a network of friends or family to turn to, this family was struggling in poverty with housing and food insecurity. By connecting with this CHEST Foundation-supported program, this patient received needed advocacy and support of doctors, social workers, and legal aid attorneys. She is now supported in an application for a monthly subsidy to help her immediate social needs while we work towards a more permanent solution. Our program has also helped patients with health-harming social needs, including lack of access to care (by helping patients apply for and enroll in Medicaid, for example), housing issues (such as mold and unresponsive landlords), and intimate partner violence. Working together as a team, we are able to provide advocacy to improve the health and well-being of our vulnerable community members. This program addresses issues that are important to my community. Without the hard work and dedication of my colleagues, the community at large, and all those committed to confronting these problems, many families would not get what they need to thrive. I am proud and feel lucky to dedicate my time to support my patients and my community. Thank you to the CHEST Foundation and all those who support it to ensure that ALL patients receive the care they deserve.”

—Drew Harris, MD

Cardiovascular Medicine and Surgery

PIONEER-HF trial: Changing practice in patients hospitalized for heart failure

Renin-angiotensin system (RAS) inhibition forms a pivotal part of guideline-recommended therapy for patients with heart failure with reduced ejection fraction (HFrEF).¹ Inhibition of the neutral endopeptidase neprilysin increases levels of several vasoactive peptides that inhibit progression of HF.² The randomized PARADIGM HF trial compared sacubitril/valsartan (angiotensin receptor neprilysin inhibition, ARNI) to enalapril in 8,434 patients with HFrEF and demonstrated a 20% reduction in the primary outcome of cardiovascular death or HF hospitalization (HR 0.80; CI 0.73– 0.87; P <.001) in patients treated with ARNI; mortality and rehospitalization were decreased significantly, as well.³ Importantly, patients had to be clinically stable and complete a sequential run-in period to be eligible for randomization. On this basis, the 2017 HF guideline update recommended transition from RAS inhibition to ARNI in trial-eligible patients.⁴

The recent PIONEER-HF trial now provides important evidence to support safety of careful initiation of sacubitril-valsartan for hospitalized patients with and without prior exposure to RAS.⁵ Hemodynamically stable patients were started on a regimen of sacubitril-valsartan, usually at doses half of those used in PARADIGM-HF. The primary endpoint of a decrease in BNP levels was improved significantly with sacubitril-valsartan (ratio 0.71, CI 0.63–0.81; P<.001), and this translated into a significant decrease in the important patient-centered secondary endpoint of rehospitalization.5 ARNI are underutilized in eligible patients; complexity of outpatient drug initiation may contribute.⁶

Data from this important trial suggest that clinicians should consider initiation of ARNI during hospitalization for acute heart failure. This could increase the number of patients receiving a guideline-recommended therapy that improves outcomes.

Steven M. Hollenberg, MD, FCCP
Steering Committee Chair

References:

1. Yancy CW et al. 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147.

2. Vardeny O et al. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663.

3. McMurray JJ, et al. Angiotensin– neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993.

4. Yancy CW, et al. 2017 ACC/ AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70:776.

5. Velasquez EJ, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851. Epub ahead of print.

6. Luo N, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from get with the guidelines-heart failure (GWTG-HF). JACC Heart Fail. 2017; 5:305.
 

Pneumonia: It is NOW time to act!

The upper part of the globe is going through another winter season and this brings large numbers of patients visiting emergency departments and requiring admission to the hospital due to pneumonia and influenza. It is concerning to see that despite our knowledge that these events will occur during this season every year, there are no significant improvements in place compared to the prior year. But the most concerning aspect of all is lack of perception that pneumonia and influenza remain among the most important diseases resulting in morbidity and mortality to both children and adults (GBD 2016 Lower Respiratory Infections Collaborators. Lancet Infect Dis 2018; S1473-3099[18]30310).

Every year we read, listen or watch the alarming news regarding the increasing number of cases of influenza and pneumonia, the number of deaths, the lack of vaccine protection, the concerns about human-to-human transmission, the development of resistance, and the lack of resources to deal with this problem. We wonder why we tolerate this difficult situation over and over again? What can we do as a society to help fight this problem? What else needs to happen so we take this issue seriously? Why can we not improve the care of patients who suffer from pneumonia? We as part of the Chest Infections NetWork would like to raise the awareness of the pneumonia and influenza problem and unite with our communities to address this calamity once and for all! A recent editorial proposes a series of strategic solutions to address this situation that include increasing the overall resources, more funding for research, and the development of advocacy groups and education programs (Aliberti S, et al. Lancet Respir Med. 2018;S2213-2600(18):30470).

Marcos I. Restrepo, MD, MSc, PhD.
Steering Committee Vice-Chair

Guidelines for the management of malignant pleural effusion

A multisociety multidisciplinary panel developed recommendations for management of malignant pleural effusions (MPE) by using the PICO (Population, Intervention, Comparator, and Outcomes) format. As per these guidelines, definitive therapy is aimed at

minimizing symptoms, re-accumulation and repeated pleural interventions, and risk of interventions in asymptomatic MPE outweighing benefits. Pleural interventions were suggested for indications such as clinical staging, obtaining molecular markers, etc. (Tremblay A. J Bronchology Interv Pulmonol. 2007;14:98). Large-volume thoracentesis is suggested for symptomatic patients and for those where lung entrapment is a concern (Lan RS. Ann Intern Med. 1997;126:768). In light of available evidence, the panel noted that the outcomes of definitive therapy for symptomatic MPE are equivocal between indwelling pleural catheter (IPC) and pleurodesis. IPC, which was restricted to un-expandable lungs in the previous guidelines, are now suggested for both expandable and un-expandable lungs (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). Talc, being the most effective and widely use pleurodesis agent, is suggested to be delivered by poudrage or slurry. Higher treatment failure rates with chemical pleurodesis, as well as low Incidence rates of IPC-related cellulitis and pleural space infections, led the panel to suggest IPC for un-expanded lungs, treatment failures, and residual symptomatic loculated effusions. In patients with IPC-related infections, treatment of the infection rather than removal of the catheter was suggested unless in events where the infection failed to respond (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). In view of evidence suggesting improved safety outcomes with ultrasound-guided pleural interventions (Abusedera M, et al. J Bronchology Interv Pulmonol. 2016;23:138), ultrasound guidance was recommended.

Bharat Bajantri, MD
Steering Committee Fellow-in-Training
 

Interprofessional Team

Difficult-to-control asthma, defined as: uncontrolled asthma despite use of maximum dose inhaled corticosteroids or chronic oral corticosteroids with daily asthma symptoms, frequent exacerbations, and/or hospitalization results in a substantial medical and financial burden with a resultant decrease in quality-of-life. Extrapulmonary co-morbidities, such as obesity, nicotine use, GERD, allergic rhinitis, chronic rhinosinusitis, sleep apnea, anxiety/depression, females of older age, vocal cord dysfunction (VCD), and type 2 diabetes mellitus (T2DM) have been shown to increase exacerbation frequency, missed days of school/work, and lessened quality-of life. Of these comorbidities, that latter has garnered recent attention as a focal point for asthma management.

Cardiovascular Medicine and Surgery

PIONEER-HF trial: Changing practice in patients hospitalized for heart failure

Renin-angiotensin system (RAS) inhibition forms a pivotal part of guideline-recommended therapy for patients with heart failure with reduced ejection fraction (HFrEF).¹ Inhibition of the neutral endopeptidase neprilysin increases levels of several vasoactive peptides that inhibit progression of HF.² The randomized PARADIGM HF trial compared sacubitril/valsartan (angiotensin receptor neprilysin inhibition, ARNI) to enalapril in 8,434 patients with HFrEF and demonstrated a 20% reduction in the primary outcome of cardiovascular death or HF hospitalization (HR 0.80; CI 0.73– 0.87; P <.001) in patients treated with ARNI; mortality and rehospitalization were decreased significantly, as well.³ Importantly, patients had to be clinically stable and complete a sequential run-in period to be eligible for randomization. On this basis, the 2017 HF guideline update recommended transition from RAS inhibition to ARNI in trial-eligible patients.⁴

The recent PIONEER-HF trial now provides important evidence to support safety of careful initiation of sacubitril-valsartan for hospitalized patients with and without prior exposure to RAS.⁵ Hemodynamically stable patients were started on a regimen of sacubitril-valsartan, usually at doses half of those used in PARADIGM-HF. The primary endpoint of a decrease in BNP levels was improved significantly with sacubitril-valsartan (ratio 0.71, CI 0.63–0.81; P<.001), and this translated into a significant decrease in the important patient-centered secondary endpoint of rehospitalization.5 ARNI are underutilized in eligible patients; complexity of outpatient drug initiation may contribute.⁶

Data from this important trial suggest that clinicians should consider initiation of ARNI during hospitalization for acute heart failure. This could increase the number of patients receiving a guideline-recommended therapy that improves outcomes.

Steven M. Hollenberg, MD, FCCP
Steering Committee Chair

References:

1. Yancy CW et al. 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147.

2. Vardeny O et al. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663.

3. McMurray JJ, et al. Angiotensin– neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993.

4. Yancy CW, et al. 2017 ACC/ AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70:776.

5. Velasquez EJ, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851. Epub ahead of print.

6. Luo N, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from get with the guidelines-heart failure (GWTG-HF). JACC Heart Fail. 2017; 5:305.
 

Pneumonia: It is NOW time to act!

The upper part of the globe is going through another winter season and this brings large numbers of patients visiting emergency departments and requiring admission to the hospital due to pneumonia and influenza. It is concerning to see that despite our knowledge that these events will occur during this season every year, there are no significant improvements in place compared to the prior year. But the most concerning aspect of all is lack of perception that pneumonia and influenza remain among the most important diseases resulting in morbidity and mortality to both children and adults (GBD 2016 Lower Respiratory Infections Collaborators. Lancet Infect Dis 2018; S1473-3099[18]30310).

Every year we read, listen or watch the alarming news regarding the increasing number of cases of influenza and pneumonia, the number of deaths, the lack of vaccine protection, the concerns about human-to-human transmission, the development of resistance, and the lack of resources to deal with this problem. We wonder why we tolerate this difficult situation over and over again? What can we do as a society to help fight this problem? What else needs to happen so we take this issue seriously? Why can we not improve the care of patients who suffer from pneumonia? We as part of the Chest Infections NetWork would like to raise the awareness of the pneumonia and influenza problem and unite with our communities to address this calamity once and for all! A recent editorial proposes a series of strategic solutions to address this situation that include increasing the overall resources, more funding for research, and the development of advocacy groups and education programs (Aliberti S, et al. Lancet Respir Med. 2018;S2213-2600(18):30470).

Marcos I. Restrepo, MD, MSc, PhD.
Steering Committee Vice-Chair

Guidelines for the management of malignant pleural effusion

A multisociety multidisciplinary panel developed recommendations for management of malignant pleural effusions (MPE) by using the PICO (Population, Intervention, Comparator, and Outcomes) format. As per these guidelines, definitive therapy is aimed at

minimizing symptoms, re-accumulation and repeated pleural interventions, and risk of interventions in asymptomatic MPE outweighing benefits. Pleural interventions were suggested for indications such as clinical staging, obtaining molecular markers, etc. (Tremblay A. J Bronchology Interv Pulmonol. 2007;14:98). Large-volume thoracentesis is suggested for symptomatic patients and for those where lung entrapment is a concern (Lan RS. Ann Intern Med. 1997;126:768). In light of available evidence, the panel noted that the outcomes of definitive therapy for symptomatic MPE are equivocal between indwelling pleural catheter (IPC) and pleurodesis. IPC, which was restricted to un-expandable lungs in the previous guidelines, are now suggested for both expandable and un-expandable lungs (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). Talc, being the most effective and widely use pleurodesis agent, is suggested to be delivered by poudrage or slurry. Higher treatment failure rates with chemical pleurodesis, as well as low Incidence rates of IPC-related cellulitis and pleural space infections, led the panel to suggest IPC for un-expanded lungs, treatment failures, and residual symptomatic loculated effusions. In patients with IPC-related infections, treatment of the infection rather than removal of the catheter was suggested unless in events where the infection failed to respond (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). In view of evidence suggesting improved safety outcomes with ultrasound-guided pleural interventions (Abusedera M, et al. J Bronchology Interv Pulmonol. 2016;23:138), ultrasound guidance was recommended.

Bharat Bajantri, MD
Steering Committee Fellow-in-Training
 

Interprofessional Team

Difficult-to-control asthma, defined as: uncontrolled asthma despite use of maximum dose inhaled corticosteroids or chronic oral corticosteroids with daily asthma symptoms, frequent exacerbations, and/or hospitalization results in a substantial medical and financial burden with a resultant decrease in quality-of-life. Extrapulmonary co-morbidities, such as obesity, nicotine use, GERD, allergic rhinitis, chronic rhinosinusitis, sleep apnea, anxiety/depression, females of older age, vocal cord dysfunction (VCD), and type 2 diabetes mellitus (T2DM) have been shown to increase exacerbation frequency, missed days of school/work, and lessened quality-of life. Of these comorbidities, that latter has garnered recent attention as a focal point for asthma management.

Cardiovascular Medicine and Surgery

PIONEER-HF trial: Changing practice in patients hospitalized for heart failure

Renin-angiotensin system (RAS) inhibition forms a pivotal part of guideline-recommended therapy for patients with heart failure with reduced ejection fraction (HFrEF).¹ Inhibition of the neutral endopeptidase neprilysin increases levels of several vasoactive peptides that inhibit progression of HF.² The randomized PARADIGM HF trial compared sacubitril/valsartan (angiotensin receptor neprilysin inhibition, ARNI) to enalapril in 8,434 patients with HFrEF and demonstrated a 20% reduction in the primary outcome of cardiovascular death or HF hospitalization (HR 0.80; CI 0.73– 0.87; P <.001) in patients treated with ARNI; mortality and rehospitalization were decreased significantly, as well.³ Importantly, patients had to be clinically stable and complete a sequential run-in period to be eligible for randomization. On this basis, the 2017 HF guideline update recommended transition from RAS inhibition to ARNI in trial-eligible patients.⁴

The recent PIONEER-HF trial now provides important evidence to support safety of careful initiation of sacubitril-valsartan for hospitalized patients with and without prior exposure to RAS.⁵ Hemodynamically stable patients were started on a regimen of sacubitril-valsartan, usually at doses half of those used in PARADIGM-HF. The primary endpoint of a decrease in BNP levels was improved significantly with sacubitril-valsartan (ratio 0.71, CI 0.63–0.81; P<.001), and this translated into a significant decrease in the important patient-centered secondary endpoint of rehospitalization.5 ARNI are underutilized in eligible patients; complexity of outpatient drug initiation may contribute.⁶

Data from this important trial suggest that clinicians should consider initiation of ARNI during hospitalization for acute heart failure. This could increase the number of patients receiving a guideline-recommended therapy that improves outcomes.

Steven M. Hollenberg, MD, FCCP
Steering Committee Chair

References:

1. Yancy CW et al. 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147.

2. Vardeny O et al. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663.

3. McMurray JJ, et al. Angiotensin– neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993.

4. Yancy CW, et al. 2017 ACC/ AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70:776.

5. Velasquez EJ, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851. Epub ahead of print.

6. Luo N, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from get with the guidelines-heart failure (GWTG-HF). JACC Heart Fail. 2017; 5:305.
 

Pneumonia: It is NOW time to act!

The upper part of the globe is going through another winter season and this brings large numbers of patients visiting emergency departments and requiring admission to the hospital due to pneumonia and influenza. It is concerning to see that despite our knowledge that these events will occur during this season every year, there are no significant improvements in place compared to the prior year. But the most concerning aspect of all is lack of perception that pneumonia and influenza remain among the most important diseases resulting in morbidity and mortality to both children and adults (GBD 2016 Lower Respiratory Infections Collaborators. Lancet Infect Dis 2018; S1473-3099[18]30310).

Every year we read, listen or watch the alarming news regarding the increasing number of cases of influenza and pneumonia, the number of deaths, the lack of vaccine protection, the concerns about human-to-human transmission, the development of resistance, and the lack of resources to deal with this problem. We wonder why we tolerate this difficult situation over and over again? What can we do as a society to help fight this problem? What else needs to happen so we take this issue seriously? Why can we not improve the care of patients who suffer from pneumonia? We as part of the Chest Infections NetWork would like to raise the awareness of the pneumonia and influenza problem and unite with our communities to address this calamity once and for all! A recent editorial proposes a series of strategic solutions to address this situation that include increasing the overall resources, more funding for research, and the development of advocacy groups and education programs (Aliberti S, et al. Lancet Respir Med. 2018;S2213-2600(18):30470).

Marcos I. Restrepo, MD, MSc, PhD.
Steering Committee Vice-Chair

Guidelines for the management of malignant pleural effusion

A multisociety multidisciplinary panel developed recommendations for management of malignant pleural effusions (MPE) by using the PICO (Population, Intervention, Comparator, and Outcomes) format. As per these guidelines, definitive therapy is aimed at

minimizing symptoms, re-accumulation and repeated pleural interventions, and risk of interventions in asymptomatic MPE outweighing benefits. Pleural interventions were suggested for indications such as clinical staging, obtaining molecular markers, etc. (Tremblay A. J Bronchology Interv Pulmonol. 2007;14:98). Large-volume thoracentesis is suggested for symptomatic patients and for those where lung entrapment is a concern (Lan RS. Ann Intern Med. 1997;126:768). In light of available evidence, the panel noted that the outcomes of definitive therapy for symptomatic MPE are equivocal between indwelling pleural catheter (IPC) and pleurodesis. IPC, which was restricted to un-expandable lungs in the previous guidelines, are now suggested for both expandable and un-expandable lungs (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). Talc, being the most effective and widely use pleurodesis agent, is suggested to be delivered by poudrage or slurry. Higher treatment failure rates with chemical pleurodesis, as well as low Incidence rates of IPC-related cellulitis and pleural space infections, led the panel to suggest IPC for un-expanded lungs, treatment failures, and residual symptomatic loculated effusions. In patients with IPC-related infections, treatment of the infection rather than removal of the catheter was suggested unless in events where the infection failed to respond (Feller-Kopman, et al. Am J Respir Crit Care Med. 2018;198[7]:839). In view of evidence suggesting improved safety outcomes with ultrasound-guided pleural interventions (Abusedera M, et al. J Bronchology Interv Pulmonol. 2016;23:138), ultrasound guidance was recommended.

Bharat Bajantri, MD
Steering Committee Fellow-in-Training
 

Interprofessional Team

Difficult-to-control asthma, defined as: uncontrolled asthma despite use of maximum dose inhaled corticosteroids or chronic oral corticosteroids with daily asthma symptoms, frequent exacerbations, and/or hospitalization results in a substantial medical and financial burden with a resultant decrease in quality-of-life. Extrapulmonary co-morbidities, such as obesity, nicotine use, GERD, allergic rhinitis, chronic rhinosinusitis, sleep apnea, anxiety/depression, females of older age, vocal cord dysfunction (VCD), and type 2 diabetes mellitus (T2DM) have been shown to increase exacerbation frequency, missed days of school/work, and lessened quality-of life. Of these comorbidities, that latter has garnered recent attention as a focal point for asthma management.

We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.

We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3 years. 

We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.

We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3 years. 

We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.

We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3 years. 

The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

The SVS Foundation has extended the application deadline for its prestigious Resident Research Award to Tuesday, Jan. 22. This award is one of the most important opportunities for surgical trainees in vascular laboratories and includes the opportunity for the recipient to showcase his or her work in a podium presentation at the 2019 Vascular Annual Meeting. In addition, the recipient receives a $5,000 award. This year’s VAM is June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., outside of Washington, D.C. Find award details and guidelines here.

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

While most outcomes are similar between robotic surgery and laparoscopic surgery for sleeve gastrectomy, the robotic approach carried a greater risk of organ space infection, according to the findings from a large clinical trial of more than 100,000 patients.

The study’s authors analyzed 107,726 sleeve gastrectomy operations in the Metabolic and Bariatric Surgery Association and Quality Improvement Program data registry (MBSAQIP), 7,385 of which were robotic sleeve gastrectomy (RSG). Peter William Lundberg, MD, and his coauthors of St. Luke’s University Health Network, Bethlehem, Pa., evaluated the safety of RSG vs. laparoscopic sleeve gastrectomy (LSG). The study was the first and largest comparing the two approaches to sleeve gastrectomy, the researchers noted.

“According to the MBSAQIP database, the robotic approach demonstrates a significantly higher rate of organ space infection while trending toward a lower rate of bleeding and 30-day reoperation and intervention,” Dr. Lundberg and his coauthors said.

Overall mortality was 0.07% in both groups (P = .49). The overall rates of significant adverse events were similar in both groups – 1.3% for LSG and 1.1% for RSG (P = .14) – as were bleeding rates – 0.5% and 0.4% (P = .003), respectively. The investigators characterized the slightly lower rates for RSG as “insignificant.”

RSG, however, had three times the rate of organ space infection than did the laparoscopic approach, 0.3% vs. 0.1% (P = .79). “Considering the enthusiasm with which robotics has been adopted by some bariatric surgeons, this is a sobering finding,” Dr. Lundberg noted.

The study determined that the use of staple-line reinforcement (SLR) alone significantly reduced the rate of bleeding regardless of approach by 31% on average (P = .0005). “This risk reduction was enhanced when SLR was combined with oversewing of the staple line,” Dr. Lundberg and his colleagues noted – an average reduction of 42% (P = .0009).

RSG took longer on average, 89 minutes vs. 63 minutes (P less than .0001), and the average length of stay was almost identical, 1.7 for RSG vs. 1.6 days for LSG. Reoperation rates within 30 days were also similar: 0.7% for RSG vs. 0.8% for LSG (P = .003).

“As surgeons continue to adopt and develop new technology, ongoing monitoring and reporting of safety and outcomes data are advised to maintain the high standards for outcomes in bariatric surgery,” Dr. Lundberg and his coauthors said.

The study researchers had no financial conflicts.

SOURCE: Lundberg PW et al. Surg Obes Relat Dis. 2018 Oct 25. doi:10.1016/j.soard.2018.10.015.
 

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.

In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.

The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.

The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.

Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.

Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.

At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.

However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).

Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.

The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.

“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.

The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.

SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.