Explore the talent of Canadian artists and the culture of Toronto during CHEST Annual Meeting 2017.
Over the last decade, Toronto’s art scene has moved to the former industrial district, creating a new home for galleries, especially those of contemporary art. While Toronto’s galleries may not be very busy outside of opening nights, they allow you to visit at any time and admire the artwork at your own pace. Along with art galleries, there are many options available to experience music and performance art, as well as family-friendly activities. Here are a few places you’ll want to visit:
Art Galleries
The Power Plant (4-minute drive), one of Toronto’s most established contemporary art galleries, is located within Harbourfront in an actual power plant - one that was in operation for most of the 1900s. If you’re with young family members, a free, hands-on art workshop led by artists with activities designed around the current exhibitions is available called Power Plant: Power Kids.
Art Metropole (15-minute drive) is a nonprofit organization with an eclectic collection of merchandise, including a huge selection of artist-created books, periodicals,
By Raysonho @ Open Grid Scheduler / Grid Engine (Own work)
Harbourfront Centreposters, clothing, audio, video, and more. The name is taken from the building’s original tenant, Art Metropole, which operated as one of Toronto’s earliest galleries from 1911 to the 1940s. Art Metropole has always been the leader of Toronto’s artistic community. In 1997, over 13,000 items were transferred to the National Gallery of Canada as the “Art Metropole Collection.” The works of world-renowned artists, such as Yoko Ono, Sol Lewitt, Joseph Beuys, and Marcel Duchamp, are included in the collection.
Daniel Faria Gallery (18-minute drive) is a bright contemporary art space found in a warehouse that used to be an auto body shop. A number of reputable, mostly Canadian, artists’ works are displayed by owner Daniel Faria, including works by Shannon Bool, Chris Curreri, Kristine Moran, and Coupland. Check out other neighboring galleries within walking distance, including Tomorrow Gallery and the artist-run Mercer Union.
Music and Theatre
The Rex Jazz & Blues Bar (6-minute drive) has two to three (mostly free) shows every day, about 19 shows a week, jazz jams on Tuesdays, local and international talent, and a fantastic location. This place is truly hard to beat.
Spend an evening at the Canadian Opera Company (6-minute drive). During the week of CHEST 2017, the COC will be showing The Elixir of Love, a Cinderella story presented with a twist, as a poor and uneducated young man dreams ofwinning the heart of a rich, clever, and beautiful woman.
For a wide variety of events and visual art, visit the Harbourfront Centre (4-minute drive). During your time at CHEST 2017, you’ll find options for literary arts, like the International Festival of Authors, theatre, music, shopping, and more. You may even get a chance for family skating on the Natrel Rink, which opens in November!
Note: all estimated times assume you are starting at the Metro Toronto Convention Centre.The arts and culture of Toronto are sure to inspire you, as will CHEST 2017. When you visit Toronto, October 28 to November 1, you’ll have access to cutting-edge education on pulmonary, critical care, and sleep medicine topics.
Learn more, and register today at chestmeeting.chestnet.org.
Explore the talent of Canadian artists and the culture of Toronto during CHEST Annual Meeting 2017.
Over the last decade, Toronto’s art scene has moved to the former industrial district, creating a new home for galleries, especially those of contemporary art. While Toronto’s galleries may not be very busy outside of opening nights, they allow you to visit at any time and admire the artwork at your own pace. Along with art galleries, there are many options available to experience music and performance art, as well as family-friendly activities. Here are a few places you’ll want to visit:
Art Galleries
The Power Plant (4-minute drive), one of Toronto’s most established contemporary art galleries, is located within Harbourfront in an actual power plant - one that was in operation for most of the 1900s. If you’re with young family members, a free, hands-on art workshop led by artists with activities designed around the current exhibitions is available called Power Plant: Power Kids.
Art Metropole (15-minute drive) is a nonprofit organization with an eclectic collection of merchandise, including a huge selection of artist-created books, periodicals,
By Raysonho @ Open Grid Scheduler / Grid Engine (Own work)
Harbourfront Centreposters, clothing, audio, video, and more. The name is taken from the building’s original tenant, Art Metropole, which operated as one of Toronto’s earliest galleries from 1911 to the 1940s. Art Metropole has always been the leader of Toronto’s artistic community. In 1997, over 13,000 items were transferred to the National Gallery of Canada as the “Art Metropole Collection.” The works of world-renowned artists, such as Yoko Ono, Sol Lewitt, Joseph Beuys, and Marcel Duchamp, are included in the collection.
Daniel Faria Gallery (18-minute drive) is a bright contemporary art space found in a warehouse that used to be an auto body shop. A number of reputable, mostly Canadian, artists’ works are displayed by owner Daniel Faria, including works by Shannon Bool, Chris Curreri, Kristine Moran, and Coupland. Check out other neighboring galleries within walking distance, including Tomorrow Gallery and the artist-run Mercer Union.
Music and Theatre
The Rex Jazz & Blues Bar (6-minute drive) has two to three (mostly free) shows every day, about 19 shows a week, jazz jams on Tuesdays, local and international talent, and a fantastic location. This place is truly hard to beat.
Spend an evening at the Canadian Opera Company (6-minute drive). During the week of CHEST 2017, the COC will be showing The Elixir of Love, a Cinderella story presented with a twist, as a poor and uneducated young man dreams ofwinning the heart of a rich, clever, and beautiful woman.
For a wide variety of events and visual art, visit the Harbourfront Centre (4-minute drive). During your time at CHEST 2017, you’ll find options for literary arts, like the International Festival of Authors, theatre, music, shopping, and more. You may even get a chance for family skating on the Natrel Rink, which opens in November!
Note: all estimated times assume you are starting at the Metro Toronto Convention Centre.The arts and culture of Toronto are sure to inspire you, as will CHEST 2017. When you visit Toronto, October 28 to November 1, you’ll have access to cutting-edge education on pulmonary, critical care, and sleep medicine topics.
Learn more, and register today at chestmeeting.chestnet.org.
Explore the talent of Canadian artists and the culture of Toronto during CHEST Annual Meeting 2017.
Over the last decade, Toronto’s art scene has moved to the former industrial district, creating a new home for galleries, especially those of contemporary art. While Toronto’s galleries may not be very busy outside of opening nights, they allow you to visit at any time and admire the artwork at your own pace. Along with art galleries, there are many options available to experience music and performance art, as well as family-friendly activities. Here are a few places you’ll want to visit:
Art Galleries
The Power Plant (4-minute drive), one of Toronto’s most established contemporary art galleries, is located within Harbourfront in an actual power plant - one that was in operation for most of the 1900s. If you’re with young family members, a free, hands-on art workshop led by artists with activities designed around the current exhibitions is available called Power Plant: Power Kids.
Art Metropole (15-minute drive) is a nonprofit organization with an eclectic collection of merchandise, including a huge selection of artist-created books, periodicals,
By Raysonho @ Open Grid Scheduler / Grid Engine (Own work)
Harbourfront Centreposters, clothing, audio, video, and more. The name is taken from the building’s original tenant, Art Metropole, which operated as one of Toronto’s earliest galleries from 1911 to the 1940s. Art Metropole has always been the leader of Toronto’s artistic community. In 1997, over 13,000 items were transferred to the National Gallery of Canada as the “Art Metropole Collection.” The works of world-renowned artists, such as Yoko Ono, Sol Lewitt, Joseph Beuys, and Marcel Duchamp, are included in the collection.
Daniel Faria Gallery (18-minute drive) is a bright contemporary art space found in a warehouse that used to be an auto body shop. A number of reputable, mostly Canadian, artists’ works are displayed by owner Daniel Faria, including works by Shannon Bool, Chris Curreri, Kristine Moran, and Coupland. Check out other neighboring galleries within walking distance, including Tomorrow Gallery and the artist-run Mercer Union.
Music and Theatre
The Rex Jazz & Blues Bar (6-minute drive) has two to three (mostly free) shows every day, about 19 shows a week, jazz jams on Tuesdays, local and international talent, and a fantastic location. This place is truly hard to beat.
Spend an evening at the Canadian Opera Company (6-minute drive). During the week of CHEST 2017, the COC will be showing The Elixir of Love, a Cinderella story presented with a twist, as a poor and uneducated young man dreams ofwinning the heart of a rich, clever, and beautiful woman.
For a wide variety of events and visual art, visit the Harbourfront Centre (4-minute drive). During your time at CHEST 2017, you’ll find options for literary arts, like the International Festival of Authors, theatre, music, shopping, and more. You may even get a chance for family skating on the Natrel Rink, which opens in November!
Note: all estimated times assume you are starting at the Metro Toronto Convention Centre.The arts and culture of Toronto are sure to inspire you, as will CHEST 2017. When you visit Toronto, October 28 to November 1, you’ll have access to cutting-edge education on pulmonary, critical care, and sleep medicine topics.
Learn more, and register today at chestmeeting.chestnet.org.
Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).
Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.
Dr. Fidaa ShaibOSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).
A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).
In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.
Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).
The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.
Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.
Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.
It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.
Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).
Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.
Dr. Fidaa ShaibOSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).
A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).
In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.
Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).
The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.
Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.
Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.
It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.
Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
Down syndrome (DS) is the most common chromosomal disorder with an estimated 250,700 children, teens, and adults living with DS in the United States in 2008 (CDC.gov). The life expectancy for individuals with DS has increased due to improved medical care, educational interventions, and identification and management of underlying psychiatric and behavioral problems. This has resulted in increased median age to 49 years, and the life expectancy of a 1-year-old child with DS to more than 60 to 65 years (Bittles et al. Dev Med Child Neurol. 2004;46[4]:282).
Sleep medicine specialists have been very involved in the care of the pediatric DS population but with the improved survival, more adult patients with DS are presenting to sleep clinics for their care. The complexity of caring for adult patients with DS poses a challenge to sleep specialists, especially with the paucity of literature and clinical guidelines.
Dr. Fidaa ShaibOSA is more prevalent in children with DS (30% to 55%) compared with control subjects (2%). This high OSA prevalence further increases to 90% in adults with DS and is associated with more oxygen desaturation, hypoventilation, and sleep disruption (Trois et al. J Clin Sleep Med. 2009;5[4]:317). Childhood risk factors for OSA in DS are mostly related to hypotonia, relatively large tongue, tonsillar and adenoid hypertrophy, and the small airway. Obesity, hypothyroidism, and, more importantly, advancing age contribute to the increased risk of OSA in adults with DS. Central sleep apnea is relatively rare in adults with DS (Esbensen. Int Rev Res Ment Retard. 2010;39(C):107).
A bidirectional relationship exists between sleep disorders and mood and cognitive problems in this population. The frequency of OSA diagnosis is increased in adults with DS who present with new-onset mood disorder or declining adaptive skills (Capone et al. Am J Med Genet A. 2013;161A[9]:2188). OSA in DS is associated with sleep disruption, decreased slow wave sleep, and intermittent hypoxemia that are thought to contribute to the mechanism of declining cognitive function and memory. Given that individuals with DS are genetically at increased risk for diffuse senile plaque formation in the brain (a characteristic pathologic finding in Alzheimer’s disease brain), the super-imposed sleep fragmentation and intermittent hypoxia may accelerate the cognitive decline (Fernandez et al. J Alzheimers Dis Parkinsonism. 2013;3[2]:124).
In addition, sleep in adults with DS is characterized by a high incidence of sleep fragmentation and circadian misalignment with delayed sleep onset and early morning awakenings (Esbensen. J Intellect Disabil Res. 2016;60[1]:68). The DS population is also at increased risk for developing depression, anxiety, obsessive-compulsive tendencies, and behavioral issues. It is also worth noting that there is a tenfold increase in autism spectrum disease in this population, and a rare condition of developmental regression in adolescents with DS has recently been recognized. Patients usually present with rapid, atypical loss of previously attained skills in cognition, socialization, and activities of daily living that may further complicate their care. The regression occurs with maladaptive behaviors that develop in relation to new transitions, hormonal or menstrual changes, or major life events (Jensen et al. Br Med J. 2014;349:g5596). As a result, new behavioral sleep problems may emerge, or challenges to the treatment of existing sleep disorders may ensue. All of the aforementioned conditions alone or in combination pose additional challenges for the management of sleep problems in this population.
Adults with DS continue to manifest the same spectrum of health problems as children with DS. Adults with DS also tend toward premature aging, which puts them at risk for additional health problems seen in the geriatric population (Covelli et al. Int J Rehabil Res. 2016;39[1]:20). Adults with DS will age earlier and two times faster than control subjects (Nakamura et al. Mech Ageing Dev. 1998;05:89). Coexisting obesity and worsening cognitive function that further increase after the age of 40 will make multiple aspects of medical management very challenging (Carfi et al. Front Med. 2014;1:51).
The care of the adult patient with DS can be best delivered through a multidisciplinary team, led by physicians well informed about the specific needs of this population. The role of the sleep specialist is essential, given the implications of sleep on health and cognitive and behavioral function. The approach to diagnosing disorders of sleep timing, quality, and duration includes a focused history. Incorporating actigraphic monitoring provides additional information that can be relevant and useful. The value of the parent-reported sleep diary becomes less and less reliable as patients enter adolescence and adulthood. Attended sleep studies are widely utilized for diagnosing sleep-disordered breathing, but their value in guiding therapy is debatable. There are multiple factors that can affect the validity of a single night of sleep testing for the individual patient. Such factors include poor sleep achieved in a strange environment and sleep position variations when compared with sleep at home. There is no evidence yet to support the use of portable sleep testing in this population.
Establishing and maintaining routines are critical in different aspects of the care of this special population, particularly in relation to behavioral sleep problems. Success is dependent on the caregiver’s approach and level of involvement in their care, the individual’s intellectual ability, and the presence of other comorbidities. Management of obesity with counseling on healthy diet and participation in exercise programs are also integral parts of their care.
Although treatment with positive airway pressure (PAP) is thought to be effective in treating OSA in DS, little data are available to support its efficacy and benefits. Treatment of OSA with PAP can be very challenging. Our sleep center experience incorporates a personalized approach with gradual PAP desensitization in addition to positive feedback and a reward system to encourage and maintain use. We also utilize behavioral therapy to encourage avoidance of supine sleep in order to decrease the severity of OSA in patients who do not accept or tolerate PAP. Surgical interventions based on assessment of the upper airway during sleep through dynamic imaging or sleep endoscopy may also be considered. A recent report of hypoglossal nerve stimulation therapy in an adolescent with severe OSA suggests a potentially new alternative option for therapy (Diercks et al. Pediatrics. 2016;137(5). doi: 10.1542/peds.2015-3663.
It seems intuitive that the management of sleep disorders in adult patients with DS positively contributes to their care and promotes their overall wellbeing. Adult patients with DS continue to present particular diagnostic and therapeutic challenges that have become even more complex as their life expectancy has increased. Further research and clinical guidelines are momentously needed in order to guide the management of sleep disorders for this particularly challenging patient population.
Dr. Shaib is Associate Professor of Medicine, Medical Director, Baylor St Luke’s Center for Sleep Medicine, Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. By Dr. M. K. Glassberg et al.
Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry. By Dr. T. R. Aksamit et al.
Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy Subjects. By Dr. C. Kempeneers et al.
Evidence-Based Medicine
Interventional Pulmonology Fellowship Accreditation Standards: Executive Summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. By Dr. J. J. Mullon et al.
Giantsin Chest Medicine
Talmadge E. King Jr., MD, FCCP. By Dr. Harold R. Collard.
Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. By Dr. M. K. Glassberg et al.
Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry. By Dr. T. R. Aksamit et al.
Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy Subjects. By Dr. C. Kempeneers et al.
Evidence-Based Medicine
Interventional Pulmonology Fellowship Accreditation Standards: Executive Summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. By Dr. J. J. Mullon et al.
Giantsin Chest Medicine
Talmadge E. King Jr., MD, FCCP. By Dr. Harold R. Collard.
Original Research
Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. By Dr. M. K. Glassberg et al.
Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry. By Dr. T. R. Aksamit et al.
Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy Subjects. By Dr. C. Kempeneers et al.
Evidence-Based Medicine
Interventional Pulmonology Fellowship Accreditation Standards: Executive Summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. By Dr. J. J. Mullon et al.
Giantsin Chest Medicine
Talmadge E. King Jr., MD, FCCP. By Dr. Harold R. Collard.
Update: 8th ed IASLC lung cancer staging guidelines
The new 8th edition guidelines on the staging of non-small cell lung cancer sponsored by the International Association for the Study of Lung Cancer (IASLC), and developed jointly by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer were enacted January 1, 2017, and provide a methodologically rigorous update to staging nomenclature (Detterbeck et al. Chest. 2017;151[1]:193). The new guidelines were developed using a database comprising 94,708 patients in 16 countries, integrating clinical, pathologic, and survival data with multivariate analysis to establish prognostically significant staging subgroups.
In the new guidelines, tumor size has been divided into 1-cm increments for T classifications with new subcategories of T1a <1 cm, T1b 1-2 cm, and T1c 2-3 cm (Rami-Porta et al. J Thorac Oncol. 2015;10[7]:990). Furthermore, T2 has been broadened to include main bronchus tumors causing lobar or whole lung atelectasis extending to the hilum. Tumors with diaphragmatic involvement have been reclassified as T4. Guidance on heterogeneous nodules has also been provided, with emphasis on measurement of the solid component (based on imaging) or depth of invasion (on pathology) to determine T classification.
The N classification remains unchanged from the 7th edition. Exploratory analysis suggested prognostic significance to the number of involved N1/N2 lymph nodes; however, this requires detailed pathologic assessment and was not adopted as a staging criterion (Asamura et al. J Thorac Oncol. 2015;10[12]:1675).
Classification of metastatic disease has been modified from M1a/M1b to M1a for thoracic metastasis, M1b for single/oligometastatic extrathoracic metastasis, and the new category M1c for multiple/disseminated metastases. M1c involvement now denotes stage IVb disease, with lower survival compared to IVa disease (0% vs 10% 5-year survival (Goldstraw et al. J Thorac Oncol. 2015;11[1]:39). Application in broader cohorts, including patients undergoing bronchoscopic staging, will be needed to further validate the new guidelines.
Vivek Murthy, MD
Fellow-in-Training MemberSteering Committee
Pulmonary Physiology, Function, and Rehabilitation
6-minute walk test
The 6-minute walk test (6MWT) is a widely used measure of functional status and exercise capacity. Though it does not diagnose specific etiologies of impairment, the 6MWT provides an assessment of the overall integrated physiologic responses to exercise (Am J Respir Crit Care Med. 2002;166[1]:111). The test is a self-paced, submaximal study. Patients are instructed to “walk as far as possible for 6 minutes” with this distance (6MWD) measured as the primary outcome. 6MWD is associated with clinical outcomes in many cardiopulmonary disorders and is reliable, valid, and responsive to treatment. Normative equations provide predicted and lower limit of normal values (Singh et al. Eur Respir J. 2014;44[6]:1447). In addition to patient comorbidities, several important factors impact 6MWD interpretation. Standardization of the testing course, patient instructions, encouragement, technician assistance, walking aids, and supplemental oxygen use are important in reducing testing variability (Holland et al. Eur Respir J. 2014;44[6]:1428). A significant learning effect exists during the first several walks. An improvement of about 26 m (range 24-29 m) has been reported in patients with COPD, with the majority improving during the second test despite a short time interval lapse. Assessing for longitudinal change in serial testing is based on the minimal clinically important difference (MCID). This represents the difference in 6MWD that is perceived as important to the patient or leads to change in management. Techniques to develop these estimates are based upon statistical analysis of study sample data (distribution-based) or changes in a different, but related, clinical variable that is used as a reference (anchor-based). While minor differences in MCID are reported based on specific disease processes, a European Respiratory Society/American Thoracic Society review based on data from patients with COPD, ILD, and PAH found a MCID value of about 30 m (range 25-33 m) for adults with chronic respiratory disease, independent of specific disease, which is only slightly larger than the short term variability (Puente-Maestu et al. Eur Respir J. 2016;47[2]:429). Knowledge of these factors can assist in proper interpretation of the 6MWT.
Lana Alghothani, MD
NetWork Member
Nitin Bhatt, MD
Steering Committee Member
Pulmonary Vascular Disease
Methamphetamine-associated pulmonary hypertension (MAPAH): “tip of the iceberg”
Pulmonary hypertension (PH) is a devastating condition with serious morbidity and mortality. The Evian Classification and more recent revisions (J Am Coll Cardiol. 2013;62(25 Suppl ):D34) reclassified PH into five subgroups based upon etio-pathogenesis. Group I PH (pulmonary arterial hypertension, PAH) represents a growing list of entities, with Drugs & Toxins (Group 1.3) as a separate subgroup. This subgroup was first recognized following the discovery of an association between PH and the ingestion of the anorexigen aminorex (Gurtner HP. Schweiz Med Wochenschr. 1985;115[24]:818).
Methamphetamine (ME) as a potential etiology for PAH was first reported in 1993 (Schaiberger et al. Chest. 1993;104[2]:614). More recently, Chin et al suggested an association between stimulant use and PAH in 28.9% of their patients diagnosed with idiopathic PAH (Chest. 2006;130[6]:1657). The growing body of evidence linking ME to PAH resulted in upgrading of ME from “Possible” to “Likely” in the latest revision of the PH classification.
Recent gene sequencing data showed carboxylesterase-1, an enzyme that protects against ME-mediated pulmonary vascular injury, may be downregulated in patients with methamphetamine-associated PAH (MAPAH) (Perez et al. Am J Respir Crit Care Med. 193;2016:A2912). Furthermore, amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension (Chen PI. JCI Insight. 2017;2[2]:e90427). Importantly, Barnett et al demonstrated a poorer prognosis in MAPAH compared with individuals with idiopathic PAH, but they are less likely to be treated with infused prostanoid therapies (Circulation. 2012;126:A13817).
Amphetamine-type stimulants have become the second most widely used class of illicit drugs worldwide (United Nations Office on Drugs & Crime. World Drug Report 2012). An estimated 4.7 million Americans (2.1% of the US population) have tried MA at some time in their lives (J Psychoactive Drugs. 2000;32[2]:137). The true incidence and prevalence of MAPAH remains unknown. One can surmise that with the widespread use of ME, we are only witnessing the “tip of the iceberg.”
Vijay Balasubramanian, MD, FCCP
Steering Committee Member
Franck Rahaghi, MD, FCCP
NetWork Member
Thoracic Oncology
Immunotherapy for lung cancer
The management of non-small cell lung cancer has traditionally focused on surgical resection of early and limited stage tumors and radiation and cytotoxic chemotherapy for patients with advanced disease. Recent progress in the management of patients with metastatic lung cancer treatment has concentrated on the precise histologic diagnosis and the characterization of molecular drivers of malignant progression. Distinguishing small cell from non-small cell carcinomas, as well as differentiating adenocarcinoma from squamous cell carcinomas, enables clinicians to more effectively tailor appropriate chemotherapy. The identification of molecular mutations in EGFR (epidermal growth factor receptor) or fusions in ELM4-ALK translocations as drivers of the malignant process has facilitated tumor regression by targeting the molecular pathways with small molecular inhibitors (tyrosine-kinase inhibitors) or synthetic antibodies. Unfortunately, not all lung cancers carry activating mutations, and those that do may develop resistance to this molecular-targeted approach and show tumor progression.
Immunotherapy, an anticancer therapeutic approach that activates the host immune system to target the tumor, has historically been either a broad spectrum management utilizing immune cytokine modifiers to augment host immune activity or a directed adaptive recruitment and stimulation of host lymphocytes to attack targeted tumor cells. More recently, immunotherapy has taken a targeted molecular approach to modify immune checkpoint inhibitory pathways, the “brakes” of the immune system that tumor cells have manipulated to evade immune surveillance. Cancer cells may be attacked by activated T cells through the MHC complex and T cell receptor pathways. However, cancer cells that express a checkpoint ligand can deactivate T cells through its checkpoint pathway. Cancer cells may evade immune recognition by signaling inhibitory checkpoint receptor pathways, such as PD-1/PDL-1, or CTLA-4 receptors. Blocking the checkpoint inhibition may reactivate the immune response and enhance host immune recognition and killing of tumor cells. Infusions containing FDA-approved nivolumab (Opdivo) and pembrolizumab (Keytruda) block the PD-1 receptor checkpoint, whereas atezolizumab (Tecentriq) blocks PD-L1, the ligand that binds PD-1. These immune therapeutic approaches have been successfully utilized in a variety of solid tumors, including lung cancer and malignant melanomas. Impressive clinical results of prolonged tumor regression have been demonstrated in second-line immunotherapy with improvements over chemotherapy; newer immunotherapy trials have demonstrated efficacy in the first-line setting for metastatic disease. Tumors with high PDL-1 expression and high mutational load predict improved immunotherapy outcomes. As expected, blocking checkpoint immune inhibition may lead to autoimmune-like conditions of pneumonitis, hepatitis, colitis, and dermatitis. Tumor tissue markers predictive of a therapeutic immune response are in the research phase. Immunotherapy against lung cancer adds to the therapeutic armamentarium of cancer management and provides an exciting new research arena into the biology and immunology of lung cancer.
Arnold M. Schwartz, MD, PhD, FCCP
Steering Committee Member
References
Cousin-Frankel J. Breakthrough of the year 2013: cancer immunotherapy. Science . 2013;342[6165]:1432.
Sharma P, et al. The future of immune checkpoint therapy. Science . 2015;348[6230]:56.
Garon EB, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med . 2015;372[21]:2018.
Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous cell non-small cell lung cancer. N Engl J Med . 2015;373[2]:123.
Reck M, et al. Pembrolizumab versus chemotherapy for PDL-1 positive non-small cell cancer. N Engl J Med . 2016;375[19]:1823. Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated PDL-1- positive advanced non-small cell lung cancer. Lancet . 2016;387[10027]:1540.
Update: 8th ed IASLC lung cancer staging guidelines
The new 8th edition guidelines on the staging of non-small cell lung cancer sponsored by the International Association for the Study of Lung Cancer (IASLC), and developed jointly by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer were enacted January 1, 2017, and provide a methodologically rigorous update to staging nomenclature (Detterbeck et al. Chest. 2017;151[1]:193). The new guidelines were developed using a database comprising 94,708 patients in 16 countries, integrating clinical, pathologic, and survival data with multivariate analysis to establish prognostically significant staging subgroups.
In the new guidelines, tumor size has been divided into 1-cm increments for T classifications with new subcategories of T1a <1 cm, T1b 1-2 cm, and T1c 2-3 cm (Rami-Porta et al. J Thorac Oncol. 2015;10[7]:990). Furthermore, T2 has been broadened to include main bronchus tumors causing lobar or whole lung atelectasis extending to the hilum. Tumors with diaphragmatic involvement have been reclassified as T4. Guidance on heterogeneous nodules has also been provided, with emphasis on measurement of the solid component (based on imaging) or depth of invasion (on pathology) to determine T classification.
The N classification remains unchanged from the 7th edition. Exploratory analysis suggested prognostic significance to the number of involved N1/N2 lymph nodes; however, this requires detailed pathologic assessment and was not adopted as a staging criterion (Asamura et al. J Thorac Oncol. 2015;10[12]:1675).
Classification of metastatic disease has been modified from M1a/M1b to M1a for thoracic metastasis, M1b for single/oligometastatic extrathoracic metastasis, and the new category M1c for multiple/disseminated metastases. M1c involvement now denotes stage IVb disease, with lower survival compared to IVa disease (0% vs 10% 5-year survival (Goldstraw et al. J Thorac Oncol. 2015;11[1]:39). Application in broader cohorts, including patients undergoing bronchoscopic staging, will be needed to further validate the new guidelines.
Vivek Murthy, MD
Fellow-in-Training MemberSteering Committee
Pulmonary Physiology, Function, and Rehabilitation
6-minute walk test
The 6-minute walk test (6MWT) is a widely used measure of functional status and exercise capacity. Though it does not diagnose specific etiologies of impairment, the 6MWT provides an assessment of the overall integrated physiologic responses to exercise (Am J Respir Crit Care Med. 2002;166[1]:111). The test is a self-paced, submaximal study. Patients are instructed to “walk as far as possible for 6 minutes” with this distance (6MWD) measured as the primary outcome. 6MWD is associated with clinical outcomes in many cardiopulmonary disorders and is reliable, valid, and responsive to treatment. Normative equations provide predicted and lower limit of normal values (Singh et al. Eur Respir J. 2014;44[6]:1447). In addition to patient comorbidities, several important factors impact 6MWD interpretation. Standardization of the testing course, patient instructions, encouragement, technician assistance, walking aids, and supplemental oxygen use are important in reducing testing variability (Holland et al. Eur Respir J. 2014;44[6]:1428). A significant learning effect exists during the first several walks. An improvement of about 26 m (range 24-29 m) has been reported in patients with COPD, with the majority improving during the second test despite a short time interval lapse. Assessing for longitudinal change in serial testing is based on the minimal clinically important difference (MCID). This represents the difference in 6MWD that is perceived as important to the patient or leads to change in management. Techniques to develop these estimates are based upon statistical analysis of study sample data (distribution-based) or changes in a different, but related, clinical variable that is used as a reference (anchor-based). While minor differences in MCID are reported based on specific disease processes, a European Respiratory Society/American Thoracic Society review based on data from patients with COPD, ILD, and PAH found a MCID value of about 30 m (range 25-33 m) for adults with chronic respiratory disease, independent of specific disease, which is only slightly larger than the short term variability (Puente-Maestu et al. Eur Respir J. 2016;47[2]:429). Knowledge of these factors can assist in proper interpretation of the 6MWT.
Lana Alghothani, MD
NetWork Member
Nitin Bhatt, MD
Steering Committee Member
Pulmonary Vascular Disease
Methamphetamine-associated pulmonary hypertension (MAPAH): “tip of the iceberg”
Pulmonary hypertension (PH) is a devastating condition with serious morbidity and mortality. The Evian Classification and more recent revisions (J Am Coll Cardiol. 2013;62(25 Suppl ):D34) reclassified PH into five subgroups based upon etio-pathogenesis. Group I PH (pulmonary arterial hypertension, PAH) represents a growing list of entities, with Drugs & Toxins (Group 1.3) as a separate subgroup. This subgroup was first recognized following the discovery of an association between PH and the ingestion of the anorexigen aminorex (Gurtner HP. Schweiz Med Wochenschr. 1985;115[24]:818).
Methamphetamine (ME) as a potential etiology for PAH was first reported in 1993 (Schaiberger et al. Chest. 1993;104[2]:614). More recently, Chin et al suggested an association between stimulant use and PAH in 28.9% of their patients diagnosed with idiopathic PAH (Chest. 2006;130[6]:1657). The growing body of evidence linking ME to PAH resulted in upgrading of ME from “Possible” to “Likely” in the latest revision of the PH classification.
Recent gene sequencing data showed carboxylesterase-1, an enzyme that protects against ME-mediated pulmonary vascular injury, may be downregulated in patients with methamphetamine-associated PAH (MAPAH) (Perez et al. Am J Respir Crit Care Med. 193;2016:A2912). Furthermore, amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension (Chen PI. JCI Insight. 2017;2[2]:e90427). Importantly, Barnett et al demonstrated a poorer prognosis in MAPAH compared with individuals with idiopathic PAH, but they are less likely to be treated with infused prostanoid therapies (Circulation. 2012;126:A13817).
Amphetamine-type stimulants have become the second most widely used class of illicit drugs worldwide (United Nations Office on Drugs & Crime. World Drug Report 2012). An estimated 4.7 million Americans (2.1% of the US population) have tried MA at some time in their lives (J Psychoactive Drugs. 2000;32[2]:137). The true incidence and prevalence of MAPAH remains unknown. One can surmise that with the widespread use of ME, we are only witnessing the “tip of the iceberg.”
Vijay Balasubramanian, MD, FCCP
Steering Committee Member
Franck Rahaghi, MD, FCCP
NetWork Member
Thoracic Oncology
Immunotherapy for lung cancer
The management of non-small cell lung cancer has traditionally focused on surgical resection of early and limited stage tumors and radiation and cytotoxic chemotherapy for patients with advanced disease. Recent progress in the management of patients with metastatic lung cancer treatment has concentrated on the precise histologic diagnosis and the characterization of molecular drivers of malignant progression. Distinguishing small cell from non-small cell carcinomas, as well as differentiating adenocarcinoma from squamous cell carcinomas, enables clinicians to more effectively tailor appropriate chemotherapy. The identification of molecular mutations in EGFR (epidermal growth factor receptor) or fusions in ELM4-ALK translocations as drivers of the malignant process has facilitated tumor regression by targeting the molecular pathways with small molecular inhibitors (tyrosine-kinase inhibitors) or synthetic antibodies. Unfortunately, not all lung cancers carry activating mutations, and those that do may develop resistance to this molecular-targeted approach and show tumor progression.
Immunotherapy, an anticancer therapeutic approach that activates the host immune system to target the tumor, has historically been either a broad spectrum management utilizing immune cytokine modifiers to augment host immune activity or a directed adaptive recruitment and stimulation of host lymphocytes to attack targeted tumor cells. More recently, immunotherapy has taken a targeted molecular approach to modify immune checkpoint inhibitory pathways, the “brakes” of the immune system that tumor cells have manipulated to evade immune surveillance. Cancer cells may be attacked by activated T cells through the MHC complex and T cell receptor pathways. However, cancer cells that express a checkpoint ligand can deactivate T cells through its checkpoint pathway. Cancer cells may evade immune recognition by signaling inhibitory checkpoint receptor pathways, such as PD-1/PDL-1, or CTLA-4 receptors. Blocking the checkpoint inhibition may reactivate the immune response and enhance host immune recognition and killing of tumor cells. Infusions containing FDA-approved nivolumab (Opdivo) and pembrolizumab (Keytruda) block the PD-1 receptor checkpoint, whereas atezolizumab (Tecentriq) blocks PD-L1, the ligand that binds PD-1. These immune therapeutic approaches have been successfully utilized in a variety of solid tumors, including lung cancer and malignant melanomas. Impressive clinical results of prolonged tumor regression have been demonstrated in second-line immunotherapy with improvements over chemotherapy; newer immunotherapy trials have demonstrated efficacy in the first-line setting for metastatic disease. Tumors with high PDL-1 expression and high mutational load predict improved immunotherapy outcomes. As expected, blocking checkpoint immune inhibition may lead to autoimmune-like conditions of pneumonitis, hepatitis, colitis, and dermatitis. Tumor tissue markers predictive of a therapeutic immune response are in the research phase. Immunotherapy against lung cancer adds to the therapeutic armamentarium of cancer management and provides an exciting new research arena into the biology and immunology of lung cancer.
Arnold M. Schwartz, MD, PhD, FCCP
Steering Committee Member
References
Cousin-Frankel J. Breakthrough of the year 2013: cancer immunotherapy. Science . 2013;342[6165]:1432.
Sharma P, et al. The future of immune checkpoint therapy. Science . 2015;348[6230]:56.
Garon EB, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med . 2015;372[21]:2018.
Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous cell non-small cell lung cancer. N Engl J Med . 2015;373[2]:123.
Reck M, et al. Pembrolizumab versus chemotherapy for PDL-1 positive non-small cell cancer. N Engl J Med . 2016;375[19]:1823. Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated PDL-1- positive advanced non-small cell lung cancer. Lancet . 2016;387[10027]:1540.
Interventional Chest/Diagnostic Procedures
Update: 8th ed IASLC lung cancer staging guidelines
The new 8th edition guidelines on the staging of non-small cell lung cancer sponsored by the International Association for the Study of Lung Cancer (IASLC), and developed jointly by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer were enacted January 1, 2017, and provide a methodologically rigorous update to staging nomenclature (Detterbeck et al. Chest. 2017;151[1]:193). The new guidelines were developed using a database comprising 94,708 patients in 16 countries, integrating clinical, pathologic, and survival data with multivariate analysis to establish prognostically significant staging subgroups.
In the new guidelines, tumor size has been divided into 1-cm increments for T classifications with new subcategories of T1a <1 cm, T1b 1-2 cm, and T1c 2-3 cm (Rami-Porta et al. J Thorac Oncol. 2015;10[7]:990). Furthermore, T2 has been broadened to include main bronchus tumors causing lobar or whole lung atelectasis extending to the hilum. Tumors with diaphragmatic involvement have been reclassified as T4. Guidance on heterogeneous nodules has also been provided, with emphasis on measurement of the solid component (based on imaging) or depth of invasion (on pathology) to determine T classification.
The N classification remains unchanged from the 7th edition. Exploratory analysis suggested prognostic significance to the number of involved N1/N2 lymph nodes; however, this requires detailed pathologic assessment and was not adopted as a staging criterion (Asamura et al. J Thorac Oncol. 2015;10[12]:1675).
Classification of metastatic disease has been modified from M1a/M1b to M1a for thoracic metastasis, M1b for single/oligometastatic extrathoracic metastasis, and the new category M1c for multiple/disseminated metastases. M1c involvement now denotes stage IVb disease, with lower survival compared to IVa disease (0% vs 10% 5-year survival (Goldstraw et al. J Thorac Oncol. 2015;11[1]:39). Application in broader cohorts, including patients undergoing bronchoscopic staging, will be needed to further validate the new guidelines.
Vivek Murthy, MD
Fellow-in-Training MemberSteering Committee
Pulmonary Physiology, Function, and Rehabilitation
6-minute walk test
The 6-minute walk test (6MWT) is a widely used measure of functional status and exercise capacity. Though it does not diagnose specific etiologies of impairment, the 6MWT provides an assessment of the overall integrated physiologic responses to exercise (Am J Respir Crit Care Med. 2002;166[1]:111). The test is a self-paced, submaximal study. Patients are instructed to “walk as far as possible for 6 minutes” with this distance (6MWD) measured as the primary outcome. 6MWD is associated with clinical outcomes in many cardiopulmonary disorders and is reliable, valid, and responsive to treatment. Normative equations provide predicted and lower limit of normal values (Singh et al. Eur Respir J. 2014;44[6]:1447). In addition to patient comorbidities, several important factors impact 6MWD interpretation. Standardization of the testing course, patient instructions, encouragement, technician assistance, walking aids, and supplemental oxygen use are important in reducing testing variability (Holland et al. Eur Respir J. 2014;44[6]:1428). A significant learning effect exists during the first several walks. An improvement of about 26 m (range 24-29 m) has been reported in patients with COPD, with the majority improving during the second test despite a short time interval lapse. Assessing for longitudinal change in serial testing is based on the minimal clinically important difference (MCID). This represents the difference in 6MWD that is perceived as important to the patient or leads to change in management. Techniques to develop these estimates are based upon statistical analysis of study sample data (distribution-based) or changes in a different, but related, clinical variable that is used as a reference (anchor-based). While minor differences in MCID are reported based on specific disease processes, a European Respiratory Society/American Thoracic Society review based on data from patients with COPD, ILD, and PAH found a MCID value of about 30 m (range 25-33 m) for adults with chronic respiratory disease, independent of specific disease, which is only slightly larger than the short term variability (Puente-Maestu et al. Eur Respir J. 2016;47[2]:429). Knowledge of these factors can assist in proper interpretation of the 6MWT.
Lana Alghothani, MD
NetWork Member
Nitin Bhatt, MD
Steering Committee Member
Pulmonary Vascular Disease
Methamphetamine-associated pulmonary hypertension (MAPAH): “tip of the iceberg”
Pulmonary hypertension (PH) is a devastating condition with serious morbidity and mortality. The Evian Classification and more recent revisions (J Am Coll Cardiol. 2013;62(25 Suppl ):D34) reclassified PH into five subgroups based upon etio-pathogenesis. Group I PH (pulmonary arterial hypertension, PAH) represents a growing list of entities, with Drugs & Toxins (Group 1.3) as a separate subgroup. This subgroup was first recognized following the discovery of an association between PH and the ingestion of the anorexigen aminorex (Gurtner HP. Schweiz Med Wochenschr. 1985;115[24]:818).
Methamphetamine (ME) as a potential etiology for PAH was first reported in 1993 (Schaiberger et al. Chest. 1993;104[2]:614). More recently, Chin et al suggested an association between stimulant use and PAH in 28.9% of their patients diagnosed with idiopathic PAH (Chest. 2006;130[6]:1657). The growing body of evidence linking ME to PAH resulted in upgrading of ME from “Possible” to “Likely” in the latest revision of the PH classification.
Recent gene sequencing data showed carboxylesterase-1, an enzyme that protects against ME-mediated pulmonary vascular injury, may be downregulated in patients with methamphetamine-associated PAH (MAPAH) (Perez et al. Am J Respir Crit Care Med. 193;2016:A2912). Furthermore, amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension (Chen PI. JCI Insight. 2017;2[2]:e90427). Importantly, Barnett et al demonstrated a poorer prognosis in MAPAH compared with individuals with idiopathic PAH, but they are less likely to be treated with infused prostanoid therapies (Circulation. 2012;126:A13817).
Amphetamine-type stimulants have become the second most widely used class of illicit drugs worldwide (United Nations Office on Drugs & Crime. World Drug Report 2012). An estimated 4.7 million Americans (2.1% of the US population) have tried MA at some time in their lives (J Psychoactive Drugs. 2000;32[2]:137). The true incidence and prevalence of MAPAH remains unknown. One can surmise that with the widespread use of ME, we are only witnessing the “tip of the iceberg.”
Vijay Balasubramanian, MD, FCCP
Steering Committee Member
Franck Rahaghi, MD, FCCP
NetWork Member
Thoracic Oncology
Immunotherapy for lung cancer
The management of non-small cell lung cancer has traditionally focused on surgical resection of early and limited stage tumors and radiation and cytotoxic chemotherapy for patients with advanced disease. Recent progress in the management of patients with metastatic lung cancer treatment has concentrated on the precise histologic diagnosis and the characterization of molecular drivers of malignant progression. Distinguishing small cell from non-small cell carcinomas, as well as differentiating adenocarcinoma from squamous cell carcinomas, enables clinicians to more effectively tailor appropriate chemotherapy. The identification of molecular mutations in EGFR (epidermal growth factor receptor) or fusions in ELM4-ALK translocations as drivers of the malignant process has facilitated tumor regression by targeting the molecular pathways with small molecular inhibitors (tyrosine-kinase inhibitors) or synthetic antibodies. Unfortunately, not all lung cancers carry activating mutations, and those that do may develop resistance to this molecular-targeted approach and show tumor progression.
Immunotherapy, an anticancer therapeutic approach that activates the host immune system to target the tumor, has historically been either a broad spectrum management utilizing immune cytokine modifiers to augment host immune activity or a directed adaptive recruitment and stimulation of host lymphocytes to attack targeted tumor cells. More recently, immunotherapy has taken a targeted molecular approach to modify immune checkpoint inhibitory pathways, the “brakes” of the immune system that tumor cells have manipulated to evade immune surveillance. Cancer cells may be attacked by activated T cells through the MHC complex and T cell receptor pathways. However, cancer cells that express a checkpoint ligand can deactivate T cells through its checkpoint pathway. Cancer cells may evade immune recognition by signaling inhibitory checkpoint receptor pathways, such as PD-1/PDL-1, or CTLA-4 receptors. Blocking the checkpoint inhibition may reactivate the immune response and enhance host immune recognition and killing of tumor cells. Infusions containing FDA-approved nivolumab (Opdivo) and pembrolizumab (Keytruda) block the PD-1 receptor checkpoint, whereas atezolizumab (Tecentriq) blocks PD-L1, the ligand that binds PD-1. These immune therapeutic approaches have been successfully utilized in a variety of solid tumors, including lung cancer and malignant melanomas. Impressive clinical results of prolonged tumor regression have been demonstrated in second-line immunotherapy with improvements over chemotherapy; newer immunotherapy trials have demonstrated efficacy in the first-line setting for metastatic disease. Tumors with high PDL-1 expression and high mutational load predict improved immunotherapy outcomes. As expected, blocking checkpoint immune inhibition may lead to autoimmune-like conditions of pneumonitis, hepatitis, colitis, and dermatitis. Tumor tissue markers predictive of a therapeutic immune response are in the research phase. Immunotherapy against lung cancer adds to the therapeutic armamentarium of cancer management and provides an exciting new research arena into the biology and immunology of lung cancer.
Arnold M. Schwartz, MD, PhD, FCCP
Steering Committee Member
References
Cousin-Frankel J. Breakthrough of the year 2013: cancer immunotherapy. Science . 2013;342[6165]:1432.
Sharma P, et al. The future of immune checkpoint therapy. Science . 2015;348[6230]:56.
Garon EB, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med . 2015;372[21]:2018.
Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous cell non-small cell lung cancer. N Engl J Med . 2015;373[2]:123.
Reck M, et al. Pembrolizumab versus chemotherapy for PDL-1 positive non-small cell cancer. N Engl J Med . 2016;375[19]:1823. Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated PDL-1- positive advanced non-small cell lung cancer. Lancet . 2016;387[10027]:1540.
Two-dose human papillomavirus (HPV) vaccine trials appear to show effective immunological responses in teen girls, said Maddalena D’Addario of the University of Bern, Switzerland, and her associates.
In seven controlled trials in 11 countries that directly compared two-dose and three-dose HPV vaccine schedules, teen girls receiving two doses of HPV vaccine with a 6-month interval between them had noninferior antibody responses to HPV16 and HPV18 for at least 2 years, compared with girls receiving three doses.
BVDC/Fotolia.com
In one study in India, teen girls who received two or three doses of HPV vaccines developed no persistent new HPV infections. When comparing different two-dose schedules, those with longer intervals between doses had higher geometric mean concentrations of antibodies.
National Cancer Institute
A limitation to this study is that there is no established immune correlate of protection, so the clinical significance of HPV antibody concentrations is uncertain, the researchers cautioned.
Two-dose human papillomavirus (HPV) vaccine trials appear to show effective immunological responses in teen girls, said Maddalena D’Addario of the University of Bern, Switzerland, and her associates.
In seven controlled trials in 11 countries that directly compared two-dose and three-dose HPV vaccine schedules, teen girls receiving two doses of HPV vaccine with a 6-month interval between them had noninferior antibody responses to HPV16 and HPV18 for at least 2 years, compared with girls receiving three doses.
BVDC/Fotolia.com
In one study in India, teen girls who received two or three doses of HPV vaccines developed no persistent new HPV infections. When comparing different two-dose schedules, those with longer intervals between doses had higher geometric mean concentrations of antibodies.
National Cancer Institute
A limitation to this study is that there is no established immune correlate of protection, so the clinical significance of HPV antibody concentrations is uncertain, the researchers cautioned.
Two-dose human papillomavirus (HPV) vaccine trials appear to show effective immunological responses in teen girls, said Maddalena D’Addario of the University of Bern, Switzerland, and her associates.
In seven controlled trials in 11 countries that directly compared two-dose and three-dose HPV vaccine schedules, teen girls receiving two doses of HPV vaccine with a 6-month interval between them had noninferior antibody responses to HPV16 and HPV18 for at least 2 years, compared with girls receiving three doses.
BVDC/Fotolia.com
In one study in India, teen girls who received two or three doses of HPV vaccines developed no persistent new HPV infections. When comparing different two-dose schedules, those with longer intervals between doses had higher geometric mean concentrations of antibodies.
National Cancer Institute
A limitation to this study is that there is no established immune correlate of protection, so the clinical significance of HPV antibody concentrations is uncertain, the researchers cautioned.
Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with our first woman President, Dr. Deborah Shure.
Deborah Shure, MD, Master FCCP
President 1995-1996
When I began my year as President of the American College of Chest Physicians in 1995 in New York City, I became the first woman to serve in that role in the then 60-year history of the College. One major theme for my presidential year was inclusiveness. With the support of the Regents and the members of the College, we sought to increase the roles of our International Fellows and Affiliate Members, as well as the participation of all of our FCCPs. We also expanded the role of the College in global tobacco control.
Dr. Deborah Shure
With a focus on these goals, the presidential year was truly an exciting and fulfilling one. I was honored to meet so many members worldwide and, through the College, enable the support of regional meetings internationally. Our efforts in the Asia-Pacific area lent essential support to one of the early conferences on tobacco control in the Philippines (Asia Pacific Conference on Control of Tobacco, Subic, Philippines, 1998). My presentation in 1996 in Bangkok was the College’s first International Partnering for World Health Award to H.M. King Bhumibol of Thailand for his work in the prevention and treatment of chest diseases in Thailand, was an unforgettable experience.
My presidential year ended in San Francisco. Since that time, my professional life has been varied and interesting. I was fortunate to continue my academic career encompassing both clinical and basic research. In 2005, I tried a new path and worked for the FDA Center for Devices and Radiological Health, using my background in device development (the angioscope) and clinical trials. Since 2012, I have been using my clinical, academic, and regulatory experience as an independent consultant in clinical trial design.
On a personal note, my partner of many years, Aymarah Robles, MD, FCCP, and I were finally able to marry in January 2015. So, we are now a happy and official two pulmonary, Cuban-American household enjoying the culture of Little Havana and the many outdoor activities of Miami!
Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with our first woman President, Dr. Deborah Shure.
Deborah Shure, MD, Master FCCP
President 1995-1996
When I began my year as President of the American College of Chest Physicians in 1995 in New York City, I became the first woman to serve in that role in the then 60-year history of the College. One major theme for my presidential year was inclusiveness. With the support of the Regents and the members of the College, we sought to increase the roles of our International Fellows and Affiliate Members, as well as the participation of all of our FCCPs. We also expanded the role of the College in global tobacco control.
Dr. Deborah Shure
With a focus on these goals, the presidential year was truly an exciting and fulfilling one. I was honored to meet so many members worldwide and, through the College, enable the support of regional meetings internationally. Our efforts in the Asia-Pacific area lent essential support to one of the early conferences on tobacco control in the Philippines (Asia Pacific Conference on Control of Tobacco, Subic, Philippines, 1998). My presentation in 1996 in Bangkok was the College’s first International Partnering for World Health Award to H.M. King Bhumibol of Thailand for his work in the prevention and treatment of chest diseases in Thailand, was an unforgettable experience.
My presidential year ended in San Francisco. Since that time, my professional life has been varied and interesting. I was fortunate to continue my academic career encompassing both clinical and basic research. In 2005, I tried a new path and worked for the FDA Center for Devices and Radiological Health, using my background in device development (the angioscope) and clinical trials. Since 2012, I have been using my clinical, academic, and regulatory experience as an independent consultant in clinical trial design.
On a personal note, my partner of many years, Aymarah Robles, MD, FCCP, and I were finally able to marry in January 2015. So, we are now a happy and official two pulmonary, Cuban-American household enjoying the culture of Little Havana and the many outdoor activities of Miami!
Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with our first woman President, Dr. Deborah Shure.
Deborah Shure, MD, Master FCCP
President 1995-1996
When I began my year as President of the American College of Chest Physicians in 1995 in New York City, I became the first woman to serve in that role in the then 60-year history of the College. One major theme for my presidential year was inclusiveness. With the support of the Regents and the members of the College, we sought to increase the roles of our International Fellows and Affiliate Members, as well as the participation of all of our FCCPs. We also expanded the role of the College in global tobacco control.
Dr. Deborah Shure
With a focus on these goals, the presidential year was truly an exciting and fulfilling one. I was honored to meet so many members worldwide and, through the College, enable the support of regional meetings internationally. Our efforts in the Asia-Pacific area lent essential support to one of the early conferences on tobacco control in the Philippines (Asia Pacific Conference on Control of Tobacco, Subic, Philippines, 1998). My presentation in 1996 in Bangkok was the College’s first International Partnering for World Health Award to H.M. King Bhumibol of Thailand for his work in the prevention and treatment of chest diseases in Thailand, was an unforgettable experience.
My presidential year ended in San Francisco. Since that time, my professional life has been varied and interesting. I was fortunate to continue my academic career encompassing both clinical and basic research. In 2005, I tried a new path and worked for the FDA Center for Devices and Radiological Health, using my background in device development (the angioscope) and clinical trials. Since 2012, I have been using my clinical, academic, and regulatory experience as an independent consultant in clinical trial design.
On a personal note, my partner of many years, Aymarah Robles, MD, FCCP, and I were finally able to marry in January 2015. So, we are now a happy and official two pulmonary, Cuban-American household enjoying the culture of Little Havana and the many outdoor activities of Miami!
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Dr. William G. WilkoffBefore we climbed on our bikes for the ride home, Peter pointed out a half-dozen schoolmates who were twirling store-bought (or more likely Internet-purchased) Fidgets. According to Peter, Fidgets first appeared in his school after the recent spring break, and they were now all the rage.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Dr. William G. WilkoffBefore we climbed on our bikes for the ride home, Peter pointed out a half-dozen schoolmates who were twirling store-bought (or more likely Internet-purchased) Fidgets. According to Peter, Fidgets first appeared in his school after the recent spring break, and they were now all the rage.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Dr. William G. WilkoffBefore we climbed on our bikes for the ride home, Peter pointed out a half-dozen schoolmates who were twirling store-bought (or more likely Internet-purchased) Fidgets. According to Peter, Fidgets first appeared in his school after the recent spring break, and they were now all the rage.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Coadministration of meningococcal serogroup B (4CMenB) and serogroup C (MenC CRM) vaccines in infants was noninferior to administration of MenC CRM alone against MenC, and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
Courtesy CDC
There was a good immune response against MenB test strains, with 95%-97% of infants having hSBA titres of 1:4 or more after completing the primary series; it rose to 97%-100% after the booster dose, the researchers reported.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Steve Mann/Thinkstock
However, there were no “concerning safety signals identified,” wrote Dr. Safadi and his colleagues. “Although this was only a small study ... the results have paramount importance for public health vaccination policies in countries such as Brazil, where a significant burden of disease is caused by these two major disease-causing serogroups in infants and small children.”
Coadministration of meningococcal serogroup B (4CMenB) and serogroup C (MenC CRM) vaccines in infants was noninferior to administration of MenC CRM alone against MenC, and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
Courtesy CDC
There was a good immune response against MenB test strains, with 95%-97% of infants having hSBA titres of 1:4 or more after completing the primary series; it rose to 97%-100% after the booster dose, the researchers reported.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Steve Mann/Thinkstock
However, there were no “concerning safety signals identified,” wrote Dr. Safadi and his colleagues. “Although this was only a small study ... the results have paramount importance for public health vaccination policies in countries such as Brazil, where a significant burden of disease is caused by these two major disease-causing serogroups in infants and small children.”
Coadministration of meningococcal serogroup B (4CMenB) and serogroup C (MenC CRM) vaccines in infants was noninferior to administration of MenC CRM alone against MenC, and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
Courtesy CDC
There was a good immune response against MenB test strains, with 95%-97% of infants having hSBA titres of 1:4 or more after completing the primary series; it rose to 97%-100% after the booster dose, the researchers reported.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Steve Mann/Thinkstock
However, there were no “concerning safety signals identified,” wrote Dr. Safadi and his colleagues. “Although this was only a small study ... the results have paramount importance for public health vaccination policies in countries such as Brazil, where a significant burden of disease is caused by these two major disease-causing serogroups in infants and small children.”
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
Dr. Augusto LitonjuaPrevious research already has suggested that vitamin D deficiency, particularly during pregnancy, may contribute to increasing incidence of asthma through a variety of potential mechanisms, explained lead author Augusto Litonjua, MD, of the Harvard Medical School and Brigham and Women’s Hospital in Boston. These mechanisms include possible effects from insufficient vitamin D on lung growth, the microbiome, and immune cell development and regulations.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
Dr. Augusto LitonjuaPrevious research already has suggested that vitamin D deficiency, particularly during pregnancy, may contribute to increasing incidence of asthma through a variety of potential mechanisms, explained lead author Augusto Litonjua, MD, of the Harvard Medical School and Brigham and Women’s Hospital in Boston. These mechanisms include possible effects from insufficient vitamin D on lung growth, the microbiome, and immune cell development and regulations.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
Dr. Augusto LitonjuaPrevious research already has suggested that vitamin D deficiency, particularly during pregnancy, may contribute to increasing incidence of asthma through a variety of potential mechanisms, explained lead author Augusto Litonjua, MD, of the Harvard Medical School and Brigham and Women’s Hospital in Boston. These mechanisms include possible effects from insufficient vitamin D on lung growth, the microbiome, and immune cell development and regulations.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
Key clinical point: Higher levels of vitamin D3 in pregnancy led to a reduced risk of asthma or allergies in subsequent children at high risk for the condition.
Major finding:Asthma/recurrent wheeze prevalence was 20% lower among 3-year-old children of mothers supplemented with D3 during pregnancy (P = .051).
Data source: A randomized controlled trial at three clinical centers from October 2009 through January 2015, involving 881 pregnant women whose children had a high risk of asthma or allergies and 806 subsequent children.
Disclosures: The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press, and consultation fees from AstraZeneca.
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
Neil Osterweil/Frontline Medical News
Dr. Rimas LukasA subanalysis of patients enrolled in the OAK trial, comparing atezolizumab with docetaxel in patients with NSCLC, showed that patients with baseline brain metastases randomized to atezolizumab had a near doubling in overall survival, compared with patients with brain metastases assigned to docetaxel.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Neil Osterweil/Frontline Medical News
Dr. Solange Peters Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
Neil Osterweil/Frontline Medical News
Dr. Rimas LukasA subanalysis of patients enrolled in the OAK trial, comparing atezolizumab with docetaxel in patients with NSCLC, showed that patients with baseline brain metastases randomized to atezolizumab had a near doubling in overall survival, compared with patients with brain metastases assigned to docetaxel.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Neil Osterweil/Frontline Medical News
Dr. Solange Peters Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
Neil Osterweil/Frontline Medical News
Dr. Rimas LukasA subanalysis of patients enrolled in the OAK trial, comparing atezolizumab with docetaxel in patients with NSCLC, showed that patients with baseline brain metastases randomized to atezolizumab had a near doubling in overall survival, compared with patients with brain metastases assigned to docetaxel.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Neil Osterweil/Frontline Medical News
Dr. Solange Peters Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
Key clinical point: The PD-L1 inhibitor atezolizumab improved overall survival, vs. docetaxel, in patients with non–small cell lung cancer and brain metastases.
Major finding: The hazard ratio for overall survival was 0.54 for patients assigned to atezolizumab, vs. docetaxel, in the OAK trial.
Data source: Pooled safety analysis of 1452 patients and efficacy analysis of 850 patients with NSCLC with or without brain metastases.
Disclosures: The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
By Raysonho @ Open Grid Scheduler / Grid Engine (Own work)
