News From CHEST Physician®

Sleep Medicine Network

Home-Based Mechanical Ventilation & Neuromuscular Disease Section

The diaphragm plays a key a role in respiratory mechanics, particularly during the inspiratory cycle. Unilateral diaphragm paralysis (UDP) from traumatic, compressive, inflammatory, neuropathic, or iatrogenic phrenic nerve injury presents with exertional dyspnea or orthopnea, though more severe cases may present with hypoventilation, hypercapnia, and daytime fatigue. Diagnostic workup requires evaluation beyond radiography to determine if diaphragm elevation indicates paralysis with or without paradox. Severity of symptoms and degree of impairment do not consistently correlate with fluoroscopic/ultrasound findings during sniff maneuver, degree of restriction by spirometry, or supine forces. Compensatory accessory muscle use during daytime breathing can mask symptoms, and there can be severe nocturnal hypoventilation related to UDP.

For symptomatic patients, treatment recommendations require understanding of the etiology and the likelihood of resolution vs progression, or association with progressive systemic conditions. Nighttime noninvasive ventilation (NIV) is considered useful since diaphragmatic weakness worsens in supine position, and hypoventilation during REM sleep without accessory muscle support is exacerbated (Steier J, et al. Eur Respir J. 2008;32[6]:1479). However, evidence for NIV in UDP remains low quality. NIV has been proposed for ventilatory support particularly when hypercapnia is present (Wiebel M, et al. Med Klin. 1995;90[1 Suppl 1]:20). For patients with progressive neuromuscular conditions, NIV with a backup rate is strongly recommended (Steindor M, et al. Respir Care. 2021;66[3]:410; Benditt JO. Respir Care. 2019;64[6]:679), but access to respiratory assist devices is limited for isolated UDP under current reimbursement algorithms without demonstrable hypercapnia or significant restrictive spirometry. The recent ONMAP recommendations calling for use of symptom severity to support initiating NIV if FVC>80% have not yet been adopted (Morgenthaler TI, et al. Chest. 2021;160[5]:e419). Without marked spirometric restriction or hypercapnia, most patients must fail conservative PAP therapy prior to escalation to NIV, and initiation of a backup rate remains debated. Nevertheless, the only large case series evaluating the predominant features of polysomnography in UDP suggests high incidence of central apneas, suggesting a backup rate may indeed be required independent of the need to support neuromuscular function (Singh M, et al. Can J Anesthesiology. 2021;68[7]:1064). Further assessment of the features, needs, and understanding of the natural trajectory is essential to guide approach to sleep-related hypoventilation in UDP.

Landy V. Luna Diaz
Section Fellow-in-Training

Bethany L. Lussier, MD, FCCP
Section Member-at-Large

Sleep Medicine Network

Home-Based Mechanical Ventilation & Neuromuscular Disease Section

The diaphragm plays a key a role in respiratory mechanics, particularly during the inspiratory cycle. Unilateral diaphragm paralysis (UDP) from traumatic, compressive, inflammatory, neuropathic, or iatrogenic phrenic nerve injury presents with exertional dyspnea or orthopnea, though more severe cases may present with hypoventilation, hypercapnia, and daytime fatigue. Diagnostic workup requires evaluation beyond radiography to determine if diaphragm elevation indicates paralysis with or without paradox. Severity of symptoms and degree of impairment do not consistently correlate with fluoroscopic/ultrasound findings during sniff maneuver, degree of restriction by spirometry, or supine forces. Compensatory accessory muscle use during daytime breathing can mask symptoms, and there can be severe nocturnal hypoventilation related to UDP.

For symptomatic patients, treatment recommendations require understanding of the etiology and the likelihood of resolution vs progression, or association with progressive systemic conditions. Nighttime noninvasive ventilation (NIV) is considered useful since diaphragmatic weakness worsens in supine position, and hypoventilation during REM sleep without accessory muscle support is exacerbated (Steier J, et al. Eur Respir J. 2008;32[6]:1479). However, evidence for NIV in UDP remains low quality. NIV has been proposed for ventilatory support particularly when hypercapnia is present (Wiebel M, et al. Med Klin. 1995;90[1 Suppl 1]:20). For patients with progressive neuromuscular conditions, NIV with a backup rate is strongly recommended (Steindor M, et al. Respir Care. 2021;66[3]:410; Benditt JO. Respir Care. 2019;64[6]:679), but access to respiratory assist devices is limited for isolated UDP under current reimbursement algorithms without demonstrable hypercapnia or significant restrictive spirometry. The recent ONMAP recommendations calling for use of symptom severity to support initiating NIV if FVC>80% have not yet been adopted (Morgenthaler TI, et al. Chest. 2021;160[5]:e419). Without marked spirometric restriction or hypercapnia, most patients must fail conservative PAP therapy prior to escalation to NIV, and initiation of a backup rate remains debated. Nevertheless, the only large case series evaluating the predominant features of polysomnography in UDP suggests high incidence of central apneas, suggesting a backup rate may indeed be required independent of the need to support neuromuscular function (Singh M, et al. Can J Anesthesiology. 2021;68[7]:1064). Further assessment of the features, needs, and understanding of the natural trajectory is essential to guide approach to sleep-related hypoventilation in UDP.

Landy V. Luna Diaz
Section Fellow-in-Training

Bethany L. Lussier, MD, FCCP
Section Member-at-Large

Sleep Medicine Network

Home-Based Mechanical Ventilation & Neuromuscular Disease Section

The diaphragm plays a key a role in respiratory mechanics, particularly during the inspiratory cycle. Unilateral diaphragm paralysis (UDP) from traumatic, compressive, inflammatory, neuropathic, or iatrogenic phrenic nerve injury presents with exertional dyspnea or orthopnea, though more severe cases may present with hypoventilation, hypercapnia, and daytime fatigue. Diagnostic workup requires evaluation beyond radiography to determine if diaphragm elevation indicates paralysis with or without paradox. Severity of symptoms and degree of impairment do not consistently correlate with fluoroscopic/ultrasound findings during sniff maneuver, degree of restriction by spirometry, or supine forces. Compensatory accessory muscle use during daytime breathing can mask symptoms, and there can be severe nocturnal hypoventilation related to UDP.

For symptomatic patients, treatment recommendations require understanding of the etiology and the likelihood of resolution vs progression, or association with progressive systemic conditions. Nighttime noninvasive ventilation (NIV) is considered useful since diaphragmatic weakness worsens in supine position, and hypoventilation during REM sleep without accessory muscle support is exacerbated (Steier J, et al. Eur Respir J. 2008;32[6]:1479). However, evidence for NIV in UDP remains low quality. NIV has been proposed for ventilatory support particularly when hypercapnia is present (Wiebel M, et al. Med Klin. 1995;90[1 Suppl 1]:20). For patients with progressive neuromuscular conditions, NIV with a backup rate is strongly recommended (Steindor M, et al. Respir Care. 2021;66[3]:410; Benditt JO. Respir Care. 2019;64[6]:679), but access to respiratory assist devices is limited for isolated UDP under current reimbursement algorithms without demonstrable hypercapnia or significant restrictive spirometry. The recent ONMAP recommendations calling for use of symptom severity to support initiating NIV if FVC>80% have not yet been adopted (Morgenthaler TI, et al. Chest. 2021;160[5]:e419). Without marked spirometric restriction or hypercapnia, most patients must fail conservative PAP therapy prior to escalation to NIV, and initiation of a backup rate remains debated. Nevertheless, the only large case series evaluating the predominant features of polysomnography in UDP suggests high incidence of central apneas, suggesting a backup rate may indeed be required independent of the need to support neuromuscular function (Singh M, et al. Can J Anesthesiology. 2021;68[7]:1064). Further assessment of the features, needs, and understanding of the natural trajectory is essential to guide approach to sleep-related hypoventilation in UDP.

Landy V. Luna Diaz
Section Fellow-in-Training

Bethany L. Lussier, MD, FCCP
Section Member-at-Large

Diffuse Lung Disease & Lung Transplant Network

Interstitial Lung Disease Section

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease that affects an estimated 100,000 people in the United States alone. Despite the availability of two approved antifibrotic drugs, nintedanib and pirfenidone, there is still a need for effective treatments to improve patient outcomes.

The ISABELA 1 and 2 trials were two Phase III clinical trials designed to evaluate ziritaxestat, a novel autotaxin inhibitor, in patients with IPF. Unfortunately, both trials were terminated early after an interim analysis revealed a lack of efficacy and safety concerns. Specifically, neither dose of ziritaxestat showed any benefit on the rate of decline for FVC over 52 weeks. Moreover, the treatment with ziritaxestat showed no benefit on the reported secondary outcomes. Patients in the ziritaxestat groups experienced worse outcomes in terms of time to first respiratory- related hospitalization, respiratory- related mortality, and first acute IPF exacerbation. Pooled data for both trials showed higher all-cause mortality for the ziritaxestat groups in relation to placebo (Maher T, et al. JAMA. 2023;329[18]:1567).

These disappointing results highlight the challenges of developing effective treatments for IPF. The complexity of IPF as a disease, with multiple pathways contributing to its pathogenesis, makes it difficult to identify effective therapeutic targets. In addition, clinical trials for new treatments must also account for the availability of approved antifibrotic therapies, which creates an added challenge for clinical trial design.

Matthew Huang, MD
Section Fellow-in-Training

Brad Bemiss, MD
Section Member-at-Large

Diffuse Lung Disease & Lung Transplant Network

Interstitial Lung Disease Section

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease that affects an estimated 100,000 people in the United States alone. Despite the availability of two approved antifibrotic drugs, nintedanib and pirfenidone, there is still a need for effective treatments to improve patient outcomes.

The ISABELA 1 and 2 trials were two Phase III clinical trials designed to evaluate ziritaxestat, a novel autotaxin inhibitor, in patients with IPF. Unfortunately, both trials were terminated early after an interim analysis revealed a lack of efficacy and safety concerns. Specifically, neither dose of ziritaxestat showed any benefit on the rate of decline for FVC over 52 weeks. Moreover, the treatment with ziritaxestat showed no benefit on the reported secondary outcomes. Patients in the ziritaxestat groups experienced worse outcomes in terms of time to first respiratory- related hospitalization, respiratory- related mortality, and first acute IPF exacerbation. Pooled data for both trials showed higher all-cause mortality for the ziritaxestat groups in relation to placebo (Maher T, et al. JAMA. 2023;329[18]:1567).

These disappointing results highlight the challenges of developing effective treatments for IPF. The complexity of IPF as a disease, with multiple pathways contributing to its pathogenesis, makes it difficult to identify effective therapeutic targets. In addition, clinical trials for new treatments must also account for the availability of approved antifibrotic therapies, which creates an added challenge for clinical trial design.

Matthew Huang, MD
Section Fellow-in-Training

Brad Bemiss, MD
Section Member-at-Large

Diffuse Lung Disease & Lung Transplant Network

Interstitial Lung Disease Section

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease that affects an estimated 100,000 people in the United States alone. Despite the availability of two approved antifibrotic drugs, nintedanib and pirfenidone, there is still a need for effective treatments to improve patient outcomes.

The ISABELA 1 and 2 trials were two Phase III clinical trials designed to evaluate ziritaxestat, a novel autotaxin inhibitor, in patients with IPF. Unfortunately, both trials were terminated early after an interim analysis revealed a lack of efficacy and safety concerns. Specifically, neither dose of ziritaxestat showed any benefit on the rate of decline for FVC over 52 weeks. Moreover, the treatment with ziritaxestat showed no benefit on the reported secondary outcomes. Patients in the ziritaxestat groups experienced worse outcomes in terms of time to first respiratory- related hospitalization, respiratory- related mortality, and first acute IPF exacerbation. Pooled data for both trials showed higher all-cause mortality for the ziritaxestat groups in relation to placebo (Maher T, et al. JAMA. 2023;329[18]:1567).

These disappointing results highlight the challenges of developing effective treatments for IPF. The complexity of IPF as a disease, with multiple pathways contributing to its pathogenesis, makes it difficult to identify effective therapeutic targets. In addition, clinical trials for new treatments must also account for the availability of approved antifibrotic therapies, which creates an added challenge for clinical trial design.

Matthew Huang, MD
Section Fellow-in-Training

Brad Bemiss, MD
Section Member-at-Large

Airways Disorders Network

Pediatric Chest Medicine Section

For young adults with chronic health conditions, the process of transitioning to adult health care is complicated, resulting in frustration for patients and families, and clinicians, as well as increased morbidity and mortality (Varty et al. J Pediatr Nurs. 2020;55:201). As such, there have been efforts to determine practices that can minimize risk and improve satisfaction with the transition process.

The National Alliance to Advance Adolescent Health developed the “Got Transition” program with input from pediatric and adult clinicians, as well as patient advocates (White, et al. Six Core Elements of Health Care Transition™ 3.0. Washington, DC: Got Transition, The National Alliance to Advance Adolescent Health, July 2020). CF R.I.S.E is a similar program aimed specifically at improving the transition to adult care among patients with cystic fibrosis (www.cfrise.com). Got Transition provides the following recommendations pertinent to both pediatric and adult providers.

Pediatric clinics should start to assess transition readiness in early adolescence, and provide training pertinent to any skill gaps identified. This may include knowledge about condition-specific self-care skills, as well as navigation of the health care system. An individualized plan can then be developed, including timing of transition and identification of an appropriate adult provider.

The transfer should include communication between the pediatric and adult care providers prior to and, if needed, after the patient’s first appointment with the adult provider. Adult clinics can enhance the transition process by establishing a method to welcome transitioning young adult patients and orient them to the practice, addressing patient concerns regarding the transition, and assessing the patients’ self-management skills with resources provided, as needed.

Both pediatric and adult providers have a role in helping patients transition safely and smoothly from pediatric to adult care.

Sarah Cohen, MD
Section Fellow-in-Training

Airways Disorders Network

Pediatric Chest Medicine Section

For young adults with chronic health conditions, the process of transitioning to adult health care is complicated, resulting in frustration for patients and families, and clinicians, as well as increased morbidity and mortality (Varty et al. J Pediatr Nurs. 2020;55:201). As such, there have been efforts to determine practices that can minimize risk and improve satisfaction with the transition process.

The National Alliance to Advance Adolescent Health developed the “Got Transition” program with input from pediatric and adult clinicians, as well as patient advocates (White, et al. Six Core Elements of Health Care Transition™ 3.0. Washington, DC: Got Transition, The National Alliance to Advance Adolescent Health, July 2020). CF R.I.S.E is a similar program aimed specifically at improving the transition to adult care among patients with cystic fibrosis (www.cfrise.com). Got Transition provides the following recommendations pertinent to both pediatric and adult providers.

Pediatric clinics should start to assess transition readiness in early adolescence, and provide training pertinent to any skill gaps identified. This may include knowledge about condition-specific self-care skills, as well as navigation of the health care system. An individualized plan can then be developed, including timing of transition and identification of an appropriate adult provider.

The transfer should include communication between the pediatric and adult care providers prior to and, if needed, after the patient’s first appointment with the adult provider. Adult clinics can enhance the transition process by establishing a method to welcome transitioning young adult patients and orient them to the practice, addressing patient concerns regarding the transition, and assessing the patients’ self-management skills with resources provided, as needed.

Both pediatric and adult providers have a role in helping patients transition safely and smoothly from pediatric to adult care.

Sarah Cohen, MD
Section Fellow-in-Training

Airways Disorders Network

Pediatric Chest Medicine Section

For young adults with chronic health conditions, the process of transitioning to adult health care is complicated, resulting in frustration for patients and families, and clinicians, as well as increased morbidity and mortality (Varty et al. J Pediatr Nurs. 2020;55:201). As such, there have been efforts to determine practices that can minimize risk and improve satisfaction with the transition process.

The National Alliance to Advance Adolescent Health developed the “Got Transition” program with input from pediatric and adult clinicians, as well as patient advocates (White, et al. Six Core Elements of Health Care Transition™ 3.0. Washington, DC: Got Transition, The National Alliance to Advance Adolescent Health, July 2020). CF R.I.S.E is a similar program aimed specifically at improving the transition to adult care among patients with cystic fibrosis (www.cfrise.com). Got Transition provides the following recommendations pertinent to both pediatric and adult providers.

Pediatric clinics should start to assess transition readiness in early adolescence, and provide training pertinent to any skill gaps identified. This may include knowledge about condition-specific self-care skills, as well as navigation of the health care system. An individualized plan can then be developed, including timing of transition and identification of an appropriate adult provider.

The transfer should include communication between the pediatric and adult care providers prior to and, if needed, after the patient’s first appointment with the adult provider. Adult clinics can enhance the transition process by establishing a method to welcome transitioning young adult patients and orient them to the practice, addressing patient concerns regarding the transition, and assessing the patients’ self-management skills with resources provided, as needed.

Both pediatric and adult providers have a role in helping patients transition safely and smoothly from pediatric to adult care.

Sarah Cohen, MD
Section Fellow-in-Training

If you’re a regular reader of the journal CHEST^®, you may have noticed an exciting new initiative for clinicians looking to enhance their understanding of the latest advances in research, improve their clinical knowledge, and earn credits toward certification: the opportunity to earn continuing medical education (CME) credits from monthly journal issues. Launched in late 2022, this new initiative was inspired by the desire to complement the excellent clinical work already being done by readers of the journal.

“Essentially, the idea was that CHEST journal readers are doing the work to keep themselves current and stay excellent doctors, and they should get credit for that work,” said Amy Morris, MD, FCCP, Chair of the CHEST Journal CME Editorial Board. “We all have to do CME, so why not get some credit for the reading that we do on a regular basis to stay current, and add some additional value for journal readers?”

But the initiative isn’t just an opportunity to offer free credits. The goal of the CME Editorial Board is to create greater awareness of important research and offer readers regular opportunities to improve their knowledge in a wide variety of specialties and clinical areas.

“We try to rotate topics month to month, but more than that, we look for articles that either have a broad impact on current clinical practice for a lot of providers, or convey some particular new interest – a way for our readers to learn about something new and interesting,” she said. “We avoid trivia, essentially “gotcha” questions that simply ensure you read the article, but rather focus on questions that reinforce key points in the article.”

To ensure the content covers a wide breadth of topics, the CME Editorial Board – comprising leaders from pulmonary, critical care, and sleep medicine to ensure the process meets a high clinical standard – reviews articles that are slated for publication monthly and selects one or more manuscripts with impactful findings. Once the articles are selected, they are sent to a cohort of experienced question writers sourced from the Network specialty areas within CHEST to draft clinically relevant questions. The final questions and answers then are returned to the Board for a careful review of their accuracy, quality, and relevancy.

Readers can visit chestnet.org/journalcme every month to see a new selection of CME-eligible articles and access questions from past issues – an offering that will only grow more robust as the initiative progresses.

“We have a regularly accumulating collection of questions such that folks who read the journal every month will always have questions to answer, and those who prefer to do some reading and CME acquisition in bulk can find a rich database of useful, interesting articles that maybe they didn’t have a chance to read when they first came out,” said Dr. Morris.

As the initiative evolves, so too will the content selected and the questions offered – a process readers will have an integral role in guiding. After answering the questions, readers will have the opportunity to provide feedback on whether the activity achieved its learning objectives, future topics to cover, and more.

Although the initiative will evolve with this feedback, said Dr. Morris, one thing remains constant: the commitment of the team developing these resources to their fellow clinicians. “We couldn’t do this without a dedicated team and a lot of volunteer time from individuals who really care about education and clinical practice, and making the literature relevant to clinical practice. It takes a lot of time and effort, and I so appreciate the work those individuals are doing.”

To access the latest CME-eligible research, and review past questions, visit chestnet.org/journalcme.

If you’re a regular reader of the journal CHEST^®, you may have noticed an exciting new initiative for clinicians looking to enhance their understanding of the latest advances in research, improve their clinical knowledge, and earn credits toward certification: the opportunity to earn continuing medical education (CME) credits from monthly journal issues. Launched in late 2022, this new initiative was inspired by the desire to complement the excellent clinical work already being done by readers of the journal.

“Essentially, the idea was that CHEST journal readers are doing the work to keep themselves current and stay excellent doctors, and they should get credit for that work,” said Amy Morris, MD, FCCP, Chair of the CHEST Journal CME Editorial Board. “We all have to do CME, so why not get some credit for the reading that we do on a regular basis to stay current, and add some additional value for journal readers?”

But the initiative isn’t just an opportunity to offer free credits. The goal of the CME Editorial Board is to create greater awareness of important research and offer readers regular opportunities to improve their knowledge in a wide variety of specialties and clinical areas.

“We try to rotate topics month to month, but more than that, we look for articles that either have a broad impact on current clinical practice for a lot of providers, or convey some particular new interest – a way for our readers to learn about something new and interesting,” she said. “We avoid trivia, essentially “gotcha” questions that simply ensure you read the article, but rather focus on questions that reinforce key points in the article.”

To ensure the content covers a wide breadth of topics, the CME Editorial Board – comprising leaders from pulmonary, critical care, and sleep medicine to ensure the process meets a high clinical standard – reviews articles that are slated for publication monthly and selects one or more manuscripts with impactful findings. Once the articles are selected, they are sent to a cohort of experienced question writers sourced from the Network specialty areas within CHEST to draft clinically relevant questions. The final questions and answers then are returned to the Board for a careful review of their accuracy, quality, and relevancy.

Readers can visit chestnet.org/journalcme every month to see a new selection of CME-eligible articles and access questions from past issues – an offering that will only grow more robust as the initiative progresses.

“We have a regularly accumulating collection of questions such that folks who read the journal every month will always have questions to answer, and those who prefer to do some reading and CME acquisition in bulk can find a rich database of useful, interesting articles that maybe they didn’t have a chance to read when they first came out,” said Dr. Morris.

As the initiative evolves, so too will the content selected and the questions offered – a process readers will have an integral role in guiding. After answering the questions, readers will have the opportunity to provide feedback on whether the activity achieved its learning objectives, future topics to cover, and more.

Although the initiative will evolve with this feedback, said Dr. Morris, one thing remains constant: the commitment of the team developing these resources to their fellow clinicians. “We couldn’t do this without a dedicated team and a lot of volunteer time from individuals who really care about education and clinical practice, and making the literature relevant to clinical practice. It takes a lot of time and effort, and I so appreciate the work those individuals are doing.”

To access the latest CME-eligible research, and review past questions, visit chestnet.org/journalcme.

If you’re a regular reader of the journal CHEST^®, you may have noticed an exciting new initiative for clinicians looking to enhance their understanding of the latest advances in research, improve their clinical knowledge, and earn credits toward certification: the opportunity to earn continuing medical education (CME) credits from monthly journal issues. Launched in late 2022, this new initiative was inspired by the desire to complement the excellent clinical work already being done by readers of the journal.

“Essentially, the idea was that CHEST journal readers are doing the work to keep themselves current and stay excellent doctors, and they should get credit for that work,” said Amy Morris, MD, FCCP, Chair of the CHEST Journal CME Editorial Board. “We all have to do CME, so why not get some credit for the reading that we do on a regular basis to stay current, and add some additional value for journal readers?”

But the initiative isn’t just an opportunity to offer free credits. The goal of the CME Editorial Board is to create greater awareness of important research and offer readers regular opportunities to improve their knowledge in a wide variety of specialties and clinical areas.

“We try to rotate topics month to month, but more than that, we look for articles that either have a broad impact on current clinical practice for a lot of providers, or convey some particular new interest – a way for our readers to learn about something new and interesting,” she said. “We avoid trivia, essentially “gotcha” questions that simply ensure you read the article, but rather focus on questions that reinforce key points in the article.”

To ensure the content covers a wide breadth of topics, the CME Editorial Board – comprising leaders from pulmonary, critical care, and sleep medicine to ensure the process meets a high clinical standard – reviews articles that are slated for publication monthly and selects one or more manuscripts with impactful findings. Once the articles are selected, they are sent to a cohort of experienced question writers sourced from the Network specialty areas within CHEST to draft clinically relevant questions. The final questions and answers then are returned to the Board for a careful review of their accuracy, quality, and relevancy.

Readers can visit chestnet.org/journalcme every month to see a new selection of CME-eligible articles and access questions from past issues – an offering that will only grow more robust as the initiative progresses.

“We have a regularly accumulating collection of questions such that folks who read the journal every month will always have questions to answer, and those who prefer to do some reading and CME acquisition in bulk can find a rich database of useful, interesting articles that maybe they didn’t have a chance to read when they first came out,” said Dr. Morris.

As the initiative evolves, so too will the content selected and the questions offered – a process readers will have an integral role in guiding. After answering the questions, readers will have the opportunity to provide feedback on whether the activity achieved its learning objectives, future topics to cover, and more.

Although the initiative will evolve with this feedback, said Dr. Morris, one thing remains constant: the commitment of the team developing these resources to their fellow clinicians. “We couldn’t do this without a dedicated team and a lot of volunteer time from individuals who really care about education and clinical practice, and making the literature relevant to clinical practice. It takes a lot of time and effort, and I so appreciate the work those individuals are doing.”

To access the latest CME-eligible research, and review past questions, visit chestnet.org/journalcme.

Maximize your learning experiences at CHEST 2023 (October 8-11 in Hawai’i) by attending a Master Class. Taking place before and after the annual meeting, these advanced-level courses on October 7, 12, and 13 will give you a deep dive into specific clinical areas with the guidance of distinguished faculty.

Replacing the “postgraduate courses” offered in previous years, the new Master Classes are open to both CHEST 2023 registrants and nonregistrants. Faculty will explore complex topics, and you will have the opportunity to participate in intensive case-based discussions with master clinicians.

“At CHEST, we’re always looking for ways to tailor the learning experience for the folks who come to the annual meeting. These Master Classes will be particularly useful for seasoned providers who are looking for a challenging education experience,” said Education Committee Chair, Amy E. Morris, MD, FCCP.

These classes will have some didactic elements, but a lot of time will be spent reviewing challenging cases that aren’t easily addressed by guidelines or a quick read of the literature and will go beyond what’s easily found online.

“Master Classes will focus on deeper-dive learning, in-depth pathophysiology and research, and conversational, interactive discussions,” Dr. Morris said.

She encourages everyone to seize the opportunity to attend these classes taught by “true masters of clinical medicine” in Hawai’i after years of strictly virtual learning that didn’t allow for as much interactivity.

“That’s why we’re in medicine – to learn from each other. This is an opportunity not just to learn facts or new ways of doing things, but a chance to interact on a personal level with providers from around the globe and master clinicians who are not always available to us in person,” she said. “In an increasingly digital world, an opportunity like this is harder to come by these days.”

Make the most of your trip to Hawai’i with advanced learning taught by highly regarded speakers. Take a look at the Master Classes available to you this year, and add a course to your meeting registration. For more information on CHEST 2023 educational offerings, browse the preliminary program at chestmeeting.chestnet.org.
 

October 7 (held in Honolulu on O’ahu)

How I Do It – Challenging Cases in Sleep Medicine

Faculty: Babak Mokhlesi, MD, FCCP; Timothy Morgenthaler, MD, FCCP; Lauren A. Tobias, MD, FCCP; and Lisa F. Wolfe, MD.

Interstitial Lung Disease

Faculty: Ayodeji Adegunsoye, MD, FCCP; Jonathan H. Chung, MD; Tejaswini Kulkarni, MD, MBBS, FCCP; Ganesh Raghu, MD; and Mary Beth Scholand, MD, FCCP.

Advances in Lung Cancer – Rocketing Forward With the Cancer Moonshot

Faculty: A. Christine Argento, MD, FCCP; Frank C. Detterbeck, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and Lynn T. Tanoue, MD, FCCP.

Pulmonary Hypertension – Expert Didactics and Discussion

Faculty: Jean M. Elwing, MD, FCCP; Peter Leary, MD, PhD; and Namita Sood, MBBCh, FCCP.

October 12-13 (held in Wailea on Maui)

2023 Pulmonary Literature Review and Complex Case Presentations – An Interactive Course With the Masters in Pulmonology

Faculty: Doreen Addrizzo-Harris, MD, FCCP; Kevin M. Chan, MD, FCCP; Stephanie M. Levine, MD, FCCP; Diego J. Maselli, MD, FCCP; Marcos I. Restrepo, MD, PhD, FCCP; Linda Rogers, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and David J. Steiger, MBChB, FCCP.

Avoiding Catastrophic Crisis in the ICU and Mastering Critical Care

Faculty: Kristin Burkart, MD, MS, FCCP; David Janz, MD; Patricia A. Kritek, MD; Matthew E. Prekker, MD; Nida Qadir, MD; Todd W. Rice, MD, FCCP; and Jonathan Sevransky, MD, FCCP.

CHEST 2023 hands-on and inter­active learning opportunities

By experiencing the latest developments for yourself through several different kinds of interactive sessions, you’ll take home actionable information that you can apply directly to your patient care. Explore the many ticketed sessions available to add on to your CHEST 2023 registration.

Simulation sessions

Choose from 25 different sessions offering hands-on experience with procedures relevant to your clinical practice.

Problem-based learning sessions

Supplement your schedule with these unique sessions, where you’ll solve real-world clinical problems in small groups and refine your expertise on clinical topics.

Meet the Professor sessions

Connect with leading chest medicine experts during these limited-capacity discussions capped at 24 registrants per session.

Maximize your learning experiences at CHEST 2023 (October 8-11 in Hawai’i) by attending a Master Class. Taking place before and after the annual meeting, these advanced-level courses on October 7, 12, and 13 will give you a deep dive into specific clinical areas with the guidance of distinguished faculty.

Replacing the “postgraduate courses” offered in previous years, the new Master Classes are open to both CHEST 2023 registrants and nonregistrants. Faculty will explore complex topics, and you will have the opportunity to participate in intensive case-based discussions with master clinicians.

“At CHEST, we’re always looking for ways to tailor the learning experience for the folks who come to the annual meeting. These Master Classes will be particularly useful for seasoned providers who are looking for a challenging education experience,” said Education Committee Chair, Amy E. Morris, MD, FCCP.

These classes will have some didactic elements, but a lot of time will be spent reviewing challenging cases that aren’t easily addressed by guidelines or a quick read of the literature and will go beyond what’s easily found online.

“Master Classes will focus on deeper-dive learning, in-depth pathophysiology and research, and conversational, interactive discussions,” Dr. Morris said.

She encourages everyone to seize the opportunity to attend these classes taught by “true masters of clinical medicine” in Hawai’i after years of strictly virtual learning that didn’t allow for as much interactivity.

“That’s why we’re in medicine – to learn from each other. This is an opportunity not just to learn facts or new ways of doing things, but a chance to interact on a personal level with providers from around the globe and master clinicians who are not always available to us in person,” she said. “In an increasingly digital world, an opportunity like this is harder to come by these days.”

Make the most of your trip to Hawai’i with advanced learning taught by highly regarded speakers. Take a look at the Master Classes available to you this year, and add a course to your meeting registration. For more information on CHEST 2023 educational offerings, browse the preliminary program at chestmeeting.chestnet.org.
 

October 7 (held in Honolulu on O’ahu)

How I Do It – Challenging Cases in Sleep Medicine

Faculty: Babak Mokhlesi, MD, FCCP; Timothy Morgenthaler, MD, FCCP; Lauren A. Tobias, MD, FCCP; and Lisa F. Wolfe, MD.

Interstitial Lung Disease

Faculty: Ayodeji Adegunsoye, MD, FCCP; Jonathan H. Chung, MD; Tejaswini Kulkarni, MD, MBBS, FCCP; Ganesh Raghu, MD; and Mary Beth Scholand, MD, FCCP.

Advances in Lung Cancer – Rocketing Forward With the Cancer Moonshot

Faculty: A. Christine Argento, MD, FCCP; Frank C. Detterbeck, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and Lynn T. Tanoue, MD, FCCP.

Pulmonary Hypertension – Expert Didactics and Discussion

Faculty: Jean M. Elwing, MD, FCCP; Peter Leary, MD, PhD; and Namita Sood, MBBCh, FCCP.

October 12-13 (held in Wailea on Maui)

2023 Pulmonary Literature Review and Complex Case Presentations – An Interactive Course With the Masters in Pulmonology

Faculty: Doreen Addrizzo-Harris, MD, FCCP; Kevin M. Chan, MD, FCCP; Stephanie M. Levine, MD, FCCP; Diego J. Maselli, MD, FCCP; Marcos I. Restrepo, MD, PhD, FCCP; Linda Rogers, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and David J. Steiger, MBChB, FCCP.

Avoiding Catastrophic Crisis in the ICU and Mastering Critical Care

Faculty: Kristin Burkart, MD, MS, FCCP; David Janz, MD; Patricia A. Kritek, MD; Matthew E. Prekker, MD; Nida Qadir, MD; Todd W. Rice, MD, FCCP; and Jonathan Sevransky, MD, FCCP.

CHEST 2023 hands-on and inter­active learning opportunities

By experiencing the latest developments for yourself through several different kinds of interactive sessions, you’ll take home actionable information that you can apply directly to your patient care. Explore the many ticketed sessions available to add on to your CHEST 2023 registration.

Simulation sessions

Choose from 25 different sessions offering hands-on experience with procedures relevant to your clinical practice.

Problem-based learning sessions

Supplement your schedule with these unique sessions, where you’ll solve real-world clinical problems in small groups and refine your expertise on clinical topics.

Meet the Professor sessions

Connect with leading chest medicine experts during these limited-capacity discussions capped at 24 registrants per session.

Maximize your learning experiences at CHEST 2023 (October 8-11 in Hawai’i) by attending a Master Class. Taking place before and after the annual meeting, these advanced-level courses on October 7, 12, and 13 will give you a deep dive into specific clinical areas with the guidance of distinguished faculty.

Replacing the “postgraduate courses” offered in previous years, the new Master Classes are open to both CHEST 2023 registrants and nonregistrants. Faculty will explore complex topics, and you will have the opportunity to participate in intensive case-based discussions with master clinicians.

“At CHEST, we’re always looking for ways to tailor the learning experience for the folks who come to the annual meeting. These Master Classes will be particularly useful for seasoned providers who are looking for a challenging education experience,” said Education Committee Chair, Amy E. Morris, MD, FCCP.

These classes will have some didactic elements, but a lot of time will be spent reviewing challenging cases that aren’t easily addressed by guidelines or a quick read of the literature and will go beyond what’s easily found online.

“Master Classes will focus on deeper-dive learning, in-depth pathophysiology and research, and conversational, interactive discussions,” Dr. Morris said.

She encourages everyone to seize the opportunity to attend these classes taught by “true masters of clinical medicine” in Hawai’i after years of strictly virtual learning that didn’t allow for as much interactivity.

“That’s why we’re in medicine – to learn from each other. This is an opportunity not just to learn facts or new ways of doing things, but a chance to interact on a personal level with providers from around the globe and master clinicians who are not always available to us in person,” she said. “In an increasingly digital world, an opportunity like this is harder to come by these days.”

Make the most of your trip to Hawai’i with advanced learning taught by highly regarded speakers. Take a look at the Master Classes available to you this year, and add a course to your meeting registration. For more information on CHEST 2023 educational offerings, browse the preliminary program at chestmeeting.chestnet.org.
 

October 7 (held in Honolulu on O’ahu)

How I Do It – Challenging Cases in Sleep Medicine

Faculty: Babak Mokhlesi, MD, FCCP; Timothy Morgenthaler, MD, FCCP; Lauren A. Tobias, MD, FCCP; and Lisa F. Wolfe, MD.

Interstitial Lung Disease

Faculty: Ayodeji Adegunsoye, MD, FCCP; Jonathan H. Chung, MD; Tejaswini Kulkarni, MD, MBBS, FCCP; Ganesh Raghu, MD; and Mary Beth Scholand, MD, FCCP.

Advances in Lung Cancer – Rocketing Forward With the Cancer Moonshot

Faculty: A. Christine Argento, MD, FCCP; Frank C. Detterbeck, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and Lynn T. Tanoue, MD, FCCP.

Pulmonary Hypertension – Expert Didactics and Discussion

Faculty: Jean M. Elwing, MD, FCCP; Peter Leary, MD, PhD; and Namita Sood, MBBCh, FCCP.

October 12-13 (held in Wailea on Maui)

2023 Pulmonary Literature Review and Complex Case Presentations – An Interactive Course With the Masters in Pulmonology

Faculty: Doreen Addrizzo-Harris, MD, FCCP; Kevin M. Chan, MD, FCCP; Stephanie M. Levine, MD, FCCP; Diego J. Maselli, MD, FCCP; Marcos I. Restrepo, MD, PhD, FCCP; Linda Rogers, MD, FCCP; Gerard A. Silvestri, MD, Master FCCP; and David J. Steiger, MBChB, FCCP.

Avoiding Catastrophic Crisis in the ICU and Mastering Critical Care

Faculty: Kristin Burkart, MD, MS, FCCP; David Janz, MD; Patricia A. Kritek, MD; Matthew E. Prekker, MD; Nida Qadir, MD; Todd W. Rice, MD, FCCP; and Jonathan Sevransky, MD, FCCP.

CHEST 2023 hands-on and inter­active learning opportunities

By experiencing the latest developments for yourself through several different kinds of interactive sessions, you’ll take home actionable information that you can apply directly to your patient care. Explore the many ticketed sessions available to add on to your CHEST 2023 registration.

Simulation sessions

Choose from 25 different sessions offering hands-on experience with procedures relevant to your clinical practice.

Problem-based learning sessions

Supplement your schedule with these unique sessions, where you’ll solve real-world clinical problems in small groups and refine your expertise on clinical topics.

Meet the Professor sessions

Connect with leading chest medicine experts during these limited-capacity discussions capped at 24 registrants per session.

When we celebrated Women’s History Month in March, Drs. Carolyn D’Ambrosio, Aneesa Das, and I discussed our experiences as women in chest medicine and why connecting is so important. We touched on the critical role of mentors. This conversation prompted me to dedicate this President’s column to the value of mentorship. The conversation is available on the CHEST YouTube for viewing.

Pursuing a career in medicine is not something you do on your own, and I have been fortunate to have had a strong support system. I think many of us who have been successful and fulfilled in our careers can say we were blessed by having great mentors along the way.

I have been blessed in having mentors who were both within my institution and outside, but one of the most important places that I found mentors was through my involvement with CHEST. It is critically important to find a mentor or mentors who can guide you through the initial phases of your career. It is also very important to allow yourself time to be a mentor to those who need you.

To the junior faculty or trainees who have yet to connect with someone to provide guidance, I cannot stress enough the importance of getting involved in an organization like CHEST.

The best way to begin is to attend the annual meeting. Know that you are invited to approach any member of CHEST leadership, introduce yourself, and tell us that you want to get involved. (Conveniently, registration for CHEST 2023 in Hawaii just opened.)

I genuinely believe our community would say yes to anyone looking for guidance.

To my colleagues who are established in their careers, I am issuing a personal request (and a bit of a challenge). Before the upcoming annual meeting, consider who among your newer colleagues could benefit from having a mentor.

Take the time to tell them that you are there to support their development. Making that connection could mean re-establishing a relationship that got off track and that you want to re-engage.

Show how the commitment to mentorship matters by sharing a post (with a picture, if possible) on social media. Tag your post using the hashtags #CHESTMentee and #CHEST2023 to introduce them to your network. This type of exposure and support can have a lasting impact.

While attending CHEST 2023 – ideally with your mentee – be sure to add the mentoring ribbons to your badge. We will be heavily socializing these ribbons, sharing that anyone wearing the “I’m a mentor” ribbon is either open to accepting new mentees or will help facilitate a conversation that may lead to mentorship.

Beyond its incredible education opportunities, the CHEST Annual Meeting is well-known for being a welcoming environment. It’s up to us to take the extra steps to help earlier-career clinicians succeed by providing the best possible education and guidance for years to come.



Until next time,

Doreen J. Addrizzo- Harris, MD, FCCP

When we celebrated Women’s History Month in March, Drs. Carolyn D’Ambrosio, Aneesa Das, and I discussed our experiences as women in chest medicine and why connecting is so important. We touched on the critical role of mentors. This conversation prompted me to dedicate this President’s column to the value of mentorship. The conversation is available on the CHEST YouTube for viewing.

Pursuing a career in medicine is not something you do on your own, and I have been fortunate to have had a strong support system. I think many of us who have been successful and fulfilled in our careers can say we were blessed by having great mentors along the way.

I have been blessed in having mentors who were both within my institution and outside, but one of the most important places that I found mentors was through my involvement with CHEST. It is critically important to find a mentor or mentors who can guide you through the initial phases of your career. It is also very important to allow yourself time to be a mentor to those who need you.

To the junior faculty or trainees who have yet to connect with someone to provide guidance, I cannot stress enough the importance of getting involved in an organization like CHEST.

The best way to begin is to attend the annual meeting. Know that you are invited to approach any member of CHEST leadership, introduce yourself, and tell us that you want to get involved. (Conveniently, registration for CHEST 2023 in Hawaii just opened.)

I genuinely believe our community would say yes to anyone looking for guidance.

To my colleagues who are established in their careers, I am issuing a personal request (and a bit of a challenge). Before the upcoming annual meeting, consider who among your newer colleagues could benefit from having a mentor.

Take the time to tell them that you are there to support their development. Making that connection could mean re-establishing a relationship that got off track and that you want to re-engage.

Show how the commitment to mentorship matters by sharing a post (with a picture, if possible) on social media. Tag your post using the hashtags #CHESTMentee and #CHEST2023 to introduce them to your network. This type of exposure and support can have a lasting impact.

While attending CHEST 2023 – ideally with your mentee – be sure to add the mentoring ribbons to your badge. We will be heavily socializing these ribbons, sharing that anyone wearing the “I’m a mentor” ribbon is either open to accepting new mentees or will help facilitate a conversation that may lead to mentorship.

Beyond its incredible education opportunities, the CHEST Annual Meeting is well-known for being a welcoming environment. It’s up to us to take the extra steps to help earlier-career clinicians succeed by providing the best possible education and guidance for years to come.



Until next time,

Doreen J. Addrizzo- Harris, MD, FCCP

When we celebrated Women’s History Month in March, Drs. Carolyn D’Ambrosio, Aneesa Das, and I discussed our experiences as women in chest medicine and why connecting is so important. We touched on the critical role of mentors. This conversation prompted me to dedicate this President’s column to the value of mentorship. The conversation is available on the CHEST YouTube for viewing.

Pursuing a career in medicine is not something you do on your own, and I have been fortunate to have had a strong support system. I think many of us who have been successful and fulfilled in our careers can say we were blessed by having great mentors along the way.

I have been blessed in having mentors who were both within my institution and outside, but one of the most important places that I found mentors was through my involvement with CHEST. It is critically important to find a mentor or mentors who can guide you through the initial phases of your career. It is also very important to allow yourself time to be a mentor to those who need you.

To the junior faculty or trainees who have yet to connect with someone to provide guidance, I cannot stress enough the importance of getting involved in an organization like CHEST.

The best way to begin is to attend the annual meeting. Know that you are invited to approach any member of CHEST leadership, introduce yourself, and tell us that you want to get involved. (Conveniently, registration for CHEST 2023 in Hawaii just opened.)

I genuinely believe our community would say yes to anyone looking for guidance.

To my colleagues who are established in their careers, I am issuing a personal request (and a bit of a challenge). Before the upcoming annual meeting, consider who among your newer colleagues could benefit from having a mentor.

Take the time to tell them that you are there to support their development. Making that connection could mean re-establishing a relationship that got off track and that you want to re-engage.

Show how the commitment to mentorship matters by sharing a post (with a picture, if possible) on social media. Tag your post using the hashtags #CHESTMentee and #CHEST2023 to introduce them to your network. This type of exposure and support can have a lasting impact.

While attending CHEST 2023 – ideally with your mentee – be sure to add the mentoring ribbons to your badge. We will be heavily socializing these ribbons, sharing that anyone wearing the “I’m a mentor” ribbon is either open to accepting new mentees or will help facilitate a conversation that may lead to mentorship.

Beyond its incredible education opportunities, the CHEST Annual Meeting is well-known for being a welcoming environment. It’s up to us to take the extra steps to help earlier-career clinicians succeed by providing the best possible education and guidance for years to come.



Until next time,

Doreen J. Addrizzo- Harris, MD, FCCP

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

Thoracic Oncology & Chest Imaging Network

Pleural Disease Section

Lobectomy with intrathoracic nodal dissection remains the standard of care for early stage (tumor size ≤ 3.0 cm) peripheral non–small cell lung cancer (NSCLC). This practice is primarily influenced by data from the mid-1990s associating limited resection (segmentectomy or wedge resection) with increased recurrence rate and mortality compared with lobectomy (Ginsberg et al. Ann Thorac Surg. 1995;60:615). Recent advances in video and robot-assisted thoracic surgery, as well as the implementation of lung cancer screening, improvement in minimally invasive diagnostic modalities, and neoadjuvant therapies have driven the medical community to revisit the role of sublobar lung resection.

Two newly published large randomized control multicenter multinational trials (Saji et al. Lancet. 2022;399:1670 and Altorki et al. N Engl J Med. 2023;388:489) have challenged our well-established practices. They compared overall and disease-free survival sublobar to lobar resection of early stage NSCLC (tumor size ≤ 2.0 cm and negative intraoperative nodal disease) and demonstrated noninferiority of sublobar resection with respect to overall survival and disease-free survival. While the sublobar resection in the Saji et al. trial consisted strictly of segmentectomy, the majority of sublobar resections in the Altorki et al. trial were wedge resections. Interestingly, both trials chose lower cut-offs for tumor size (≤ 2.0 cm) compared with the Ginsberg trial (≤ 3.0 cm), which could arguably have accounted for this difference in outcomes. In summary, these emerging data are here to tell us a new story by supporting more limited anatomical lung resection options for our patients with early stage NSCLC.

Christopher Yurosko, DO – Section Fellow-in-Training

Melissa Rosas, MD – Section Member-at-Large

Labib Debiane, MD - Section Member-at-Large

Thoracic Oncology & Chest Imaging Network

Pleural Disease Section

Lobectomy with intrathoracic nodal dissection remains the standard of care for early stage (tumor size ≤ 3.0 cm) peripheral non–small cell lung cancer (NSCLC). This practice is primarily influenced by data from the mid-1990s associating limited resection (segmentectomy or wedge resection) with increased recurrence rate and mortality compared with lobectomy (Ginsberg et al. Ann Thorac Surg. 1995;60:615). Recent advances in video and robot-assisted thoracic surgery, as well as the implementation of lung cancer screening, improvement in minimally invasive diagnostic modalities, and neoadjuvant therapies have driven the medical community to revisit the role of sublobar lung resection.

Two newly published large randomized control multicenter multinational trials (Saji et al. Lancet. 2022;399:1670 and Altorki et al. N Engl J Med. 2023;388:489) have challenged our well-established practices. They compared overall and disease-free survival sublobar to lobar resection of early stage NSCLC (tumor size ≤ 2.0 cm and negative intraoperative nodal disease) and demonstrated noninferiority of sublobar resection with respect to overall survival and disease-free survival. While the sublobar resection in the Saji et al. trial consisted strictly of segmentectomy, the majority of sublobar resections in the Altorki et al. trial were wedge resections. Interestingly, both trials chose lower cut-offs for tumor size (≤ 2.0 cm) compared with the Ginsberg trial (≤ 3.0 cm), which could arguably have accounted for this difference in outcomes. In summary, these emerging data are here to tell us a new story by supporting more limited anatomical lung resection options for our patients with early stage NSCLC.

Christopher Yurosko, DO – Section Fellow-in-Training

Melissa Rosas, MD – Section Member-at-Large

Labib Debiane, MD - Section Member-at-Large

Thoracic Oncology & Chest Imaging Network

Pleural Disease Section

Lobectomy with intrathoracic nodal dissection remains the standard of care for early stage (tumor size ≤ 3.0 cm) peripheral non–small cell lung cancer (NSCLC). This practice is primarily influenced by data from the mid-1990s associating limited resection (segmentectomy or wedge resection) with increased recurrence rate and mortality compared with lobectomy (Ginsberg et al. Ann Thorac Surg. 1995;60:615). Recent advances in video and robot-assisted thoracic surgery, as well as the implementation of lung cancer screening, improvement in minimally invasive diagnostic modalities, and neoadjuvant therapies have driven the medical community to revisit the role of sublobar lung resection.

Two newly published large randomized control multicenter multinational trials (Saji et al. Lancet. 2022;399:1670 and Altorki et al. N Engl J Med. 2023;388:489) have challenged our well-established practices. They compared overall and disease-free survival sublobar to lobar resection of early stage NSCLC (tumor size ≤ 2.0 cm and negative intraoperative nodal disease) and demonstrated noninferiority of sublobar resection with respect to overall survival and disease-free survival. While the sublobar resection in the Saji et al. trial consisted strictly of segmentectomy, the majority of sublobar resections in the Altorki et al. trial were wedge resections. Interestingly, both trials chose lower cut-offs for tumor size (≤ 2.0 cm) compared with the Ginsberg trial (≤ 3.0 cm), which could arguably have accounted for this difference in outcomes. In summary, these emerging data are here to tell us a new story by supporting more limited anatomical lung resection options for our patients with early stage NSCLC.

Christopher Yurosko, DO – Section Fellow-in-Training

Melissa Rosas, MD – Section Member-at-Large

Labib Debiane, MD - Section Member-at-Large

Sleep Medicine Network

Non-Respiratory Sleep Section

Want to feel your best when enjoying CHEST 2023 sessions, games, vendors, networking events, and much more on the island paradise of Hawai’i? It’s time to start making plans to align your circadian rhythm with Hawai’i Standard Time (HST).

Dr. Sabra Abbott, a circadian rhythm expert and the Director of the Circadian Medicine Clinic at Northwestern University, recommends “to best adapt to the time zone change, you can take advantage of the time-of-day specific phase shifting properties of light and melatonin.”

Before heading west to the meeting, Dr. Abbott recommends mainland USA travelers get extra light exposure in the evening. On arrival in Hawai’i, morning bright-light exposure should be limited. Luckily, afternoon/early evening light exposure is encouraged, which will help get some extra hours on the beach! Don’t forget your sunglasses to help with blocking light in the morning.

Once the meeting has concluded, attendees from mainland USA will need to advance their internal clocks earlier as they travel east back home. This can be achieved by taking melatonin 0.5 mg around bedtime and seeking bright-light during the mid-to-late morning.

To develop a personalized sleep prescription based on your time zone and preferred sleep times, you can use an online jet lag calculator, such as Jet Lag Rooster (jetlag.sleepopolis.com; no affiliations with authors or Dr. Abbott).

To learn more about circadian rhythm alignment when working and traveling, we’ll see you at the CHEST 2023 session “Shifting to Hawai’i – Jet Lag, Shift Workers, and Sleep for Health Care Providers” (10/8/2023 at 0815-HST).  If you haven't registered for the meeting, make sure to do so soon! You'll find the full schedule, pricing, and more at the CHEST 2023 website.

Paul Chung, DO – Section Fellow-in-Training
Lisa Wolfe, MD – Section Member-at-Large
William Healy, MD – Section Member-at-Large

Sleep Medicine Network

Non-Respiratory Sleep Section

Want to feel your best when enjoying CHEST 2023 sessions, games, vendors, networking events, and much more on the island paradise of Hawai’i? It’s time to start making plans to align your circadian rhythm with Hawai’i Standard Time (HST).

Dr. Sabra Abbott, a circadian rhythm expert and the Director of the Circadian Medicine Clinic at Northwestern University, recommends “to best adapt to the time zone change, you can take advantage of the time-of-day specific phase shifting properties of light and melatonin.”

Before heading west to the meeting, Dr. Abbott recommends mainland USA travelers get extra light exposure in the evening. On arrival in Hawai’i, morning bright-light exposure should be limited. Luckily, afternoon/early evening light exposure is encouraged, which will help get some extra hours on the beach! Don’t forget your sunglasses to help with blocking light in the morning.

Once the meeting has concluded, attendees from mainland USA will need to advance their internal clocks earlier as they travel east back home. This can be achieved by taking melatonin 0.5 mg around bedtime and seeking bright-light during the mid-to-late morning.

To develop a personalized sleep prescription based on your time zone and preferred sleep times, you can use an online jet lag calculator, such as Jet Lag Rooster (jetlag.sleepopolis.com; no affiliations with authors or Dr. Abbott).

To learn more about circadian rhythm alignment when working and traveling, we’ll see you at the CHEST 2023 session “Shifting to Hawai’i – Jet Lag, Shift Workers, and Sleep for Health Care Providers” (10/8/2023 at 0815-HST).  If you haven't registered for the meeting, make sure to do so soon! You'll find the full schedule, pricing, and more at the CHEST 2023 website.

Paul Chung, DO – Section Fellow-in-Training
Lisa Wolfe, MD – Section Member-at-Large
William Healy, MD – Section Member-at-Large

Sleep Medicine Network

Non-Respiratory Sleep Section

Want to feel your best when enjoying CHEST 2023 sessions, games, vendors, networking events, and much more on the island paradise of Hawai’i? It’s time to start making plans to align your circadian rhythm with Hawai’i Standard Time (HST).

Dr. Sabra Abbott, a circadian rhythm expert and the Director of the Circadian Medicine Clinic at Northwestern University, recommends “to best adapt to the time zone change, you can take advantage of the time-of-day specific phase shifting properties of light and melatonin.”

Before heading west to the meeting, Dr. Abbott recommends mainland USA travelers get extra light exposure in the evening. On arrival in Hawai’i, morning bright-light exposure should be limited. Luckily, afternoon/early evening light exposure is encouraged, which will help get some extra hours on the beach! Don’t forget your sunglasses to help with blocking light in the morning.

Once the meeting has concluded, attendees from mainland USA will need to advance their internal clocks earlier as they travel east back home. This can be achieved by taking melatonin 0.5 mg around bedtime and seeking bright-light during the mid-to-late morning.

To develop a personalized sleep prescription based on your time zone and preferred sleep times, you can use an online jet lag calculator, such as Jet Lag Rooster (jetlag.sleepopolis.com; no affiliations with authors or Dr. Abbott).

To learn more about circadian rhythm alignment when working and traveling, we’ll see you at the CHEST 2023 session “Shifting to Hawai’i – Jet Lag, Shift Workers, and Sleep for Health Care Providers” (10/8/2023 at 0815-HST).  If you haven't registered for the meeting, make sure to do so soon! You'll find the full schedule, pricing, and more at the CHEST 2023 website.

Paul Chung, DO – Section Fellow-in-Training
Lisa Wolfe, MD – Section Member-at-Large
William Healy, MD – Section Member-at-Large

Pulmonary Vascular & Cardiovascular Network

Pulmonary Vascular Disease Section

The recently published STELLAR trial was a phase 3, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate patients with PAH receiving stable vasodilator therapy after treatment with sotatercept, a first-in-class recombinant fusion protein with parts of the activin receptor type IIA, a member of the BMPR2/TGF-beta superfamily of receptors and ligands (Hoeper. N Engl J Med. 2023;388:1478).

Sotatercept improved 6-minute walk distance, the primary endpoint of the trial at 24-weeks, as well as eight of the trial’s nine secondary endpoints including changes in PVR, NT-ProBNP levels, functional class, French risk score, and time-to-clinical worsening when compared with placebo. However, many questions remain about the mechanisms whereby sotatercept achieved its clinical endpoints, the answers to which may lie within its basic molecular biology.

The focus on BMPR2/TGF-beta cell signaling pathways originated from the identification of loss-of-function mutations in the BMPR2 gene in patients with heritable and idiopathic PAH (Morrell, NW. Eur Respir J. 2019;53[3]: 1900078). An imbalance in BMPR2/TGF-beta signaling (low BMPR2/high TGF-beta function) has been proposed as a central mechanism in the development of PAH. Specifically, researchers have shown increased levels of Activin A, one of 33 ligands that can bind either BMPR2 or TGF-beta receptors, within vascular lesions in the lungs of patients with PAH. It has been thus hypothesized that reducing the amount of circulating Activin A could treat PAH by rebalancing BMPR2/TGF-beta signaling in lung vascular cells. In preclinical experimental models of PAH with elevated Activin A levels, sotatercept has been shown to reduce distal small vessel medial thickness/muscularization and increase the number of patent small vessels (Yung, LM. Sci Transl Med. 2020;12).

The exact mechanism by which sotatercept improves hemodynamics and outcomes remains unclear. Indeed, whether de-remodeling of the lung vasculature or new vessel formation occurs in humans is unknown. The results from STELLAR mark a new era in the development of potential “disease-modifying agents” for PAH; however, the question is: what exactly are we modifying?

Jose Gomez-Arroyo, MD, PhD – Section Fellow-in-Training
Dana Kay, DO – Section Member-at-Large

Pulmonary Vascular & Cardiovascular Network

Pulmonary Vascular Disease Section

The recently published STELLAR trial was a phase 3, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate patients with PAH receiving stable vasodilator therapy after treatment with sotatercept, a first-in-class recombinant fusion protein with parts of the activin receptor type IIA, a member of the BMPR2/TGF-beta superfamily of receptors and ligands (Hoeper. N Engl J Med. 2023;388:1478).

Sotatercept improved 6-minute walk distance, the primary endpoint of the trial at 24-weeks, as well as eight of the trial’s nine secondary endpoints including changes in PVR, NT-ProBNP levels, functional class, French risk score, and time-to-clinical worsening when compared with placebo. However, many questions remain about the mechanisms whereby sotatercept achieved its clinical endpoints, the answers to which may lie within its basic molecular biology.

The focus on BMPR2/TGF-beta cell signaling pathways originated from the identification of loss-of-function mutations in the BMPR2 gene in patients with heritable and idiopathic PAH (Morrell, NW. Eur Respir J. 2019;53[3]: 1900078). An imbalance in BMPR2/TGF-beta signaling (low BMPR2/high TGF-beta function) has been proposed as a central mechanism in the development of PAH. Specifically, researchers have shown increased levels of Activin A, one of 33 ligands that can bind either BMPR2 or TGF-beta receptors, within vascular lesions in the lungs of patients with PAH. It has been thus hypothesized that reducing the amount of circulating Activin A could treat PAH by rebalancing BMPR2/TGF-beta signaling in lung vascular cells. In preclinical experimental models of PAH with elevated Activin A levels, sotatercept has been shown to reduce distal small vessel medial thickness/muscularization and increase the number of patent small vessels (Yung, LM. Sci Transl Med. 2020;12).

The exact mechanism by which sotatercept improves hemodynamics and outcomes remains unclear. Indeed, whether de-remodeling of the lung vasculature or new vessel formation occurs in humans is unknown. The results from STELLAR mark a new era in the development of potential “disease-modifying agents” for PAH; however, the question is: what exactly are we modifying?

Jose Gomez-Arroyo, MD, PhD – Section Fellow-in-Training
Dana Kay, DO – Section Member-at-Large

Pulmonary Vascular & Cardiovascular Network

Pulmonary Vascular Disease Section

The recently published STELLAR trial was a phase 3, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate patients with PAH receiving stable vasodilator therapy after treatment with sotatercept, a first-in-class recombinant fusion protein with parts of the activin receptor type IIA, a member of the BMPR2/TGF-beta superfamily of receptors and ligands (Hoeper. N Engl J Med. 2023;388:1478).

Sotatercept improved 6-minute walk distance, the primary endpoint of the trial at 24-weeks, as well as eight of the trial’s nine secondary endpoints including changes in PVR, NT-ProBNP levels, functional class, French risk score, and time-to-clinical worsening when compared with placebo. However, many questions remain about the mechanisms whereby sotatercept achieved its clinical endpoints, the answers to which may lie within its basic molecular biology.

The focus on BMPR2/TGF-beta cell signaling pathways originated from the identification of loss-of-function mutations in the BMPR2 gene in patients with heritable and idiopathic PAH (Morrell, NW. Eur Respir J. 2019;53[3]: 1900078). An imbalance in BMPR2/TGF-beta signaling (low BMPR2/high TGF-beta function) has been proposed as a central mechanism in the development of PAH. Specifically, researchers have shown increased levels of Activin A, one of 33 ligands that can bind either BMPR2 or TGF-beta receptors, within vascular lesions in the lungs of patients with PAH. It has been thus hypothesized that reducing the amount of circulating Activin A could treat PAH by rebalancing BMPR2/TGF-beta signaling in lung vascular cells. In preclinical experimental models of PAH with elevated Activin A levels, sotatercept has been shown to reduce distal small vessel medial thickness/muscularization and increase the number of patent small vessels (Yung, LM. Sci Transl Med. 2020;12).

The exact mechanism by which sotatercept improves hemodynamics and outcomes remains unclear. Indeed, whether de-remodeling of the lung vasculature or new vessel formation occurs in humans is unknown. The results from STELLAR mark a new era in the development of potential “disease-modifying agents” for PAH; however, the question is: what exactly are we modifying?

Jose Gomez-Arroyo, MD, PhD – Section Fellow-in-Training
Dana Kay, DO – Section Member-at-Large