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Giving the Smallest GI Transplant Patients a New Lease On Life
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
Should napping be recommended as a health behavior?
I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.
Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.
Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.
Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.
In the second context, epidemiological studies examining the impact of napping on health outcomes are typically conducted in older, less healthy, less active populations who tend to have poorer eating habits, multiple comorbidities, psychological problems, and a wide range of socioeconomic status. The strength of this approach is the sample size, which allows for correlations between factors on a large scale while providing enough data to hopefully control for possible confounds (eg, demographics, SES, exercise and eating habits, comorbidities). However, as the data were usually collected by a different group with different goals than the current epidemiologist exploring the data, there can be a disconnect between the current study goals and the variables that were initially collected by the original research team. As such, the current researcher is left with a patchwork of dissimilar variables that they must find a way to organize to answer the current question.3
When applied to the question of health effects of napping, epidemiology researchers typically divide the population into two groups, either based on a yes or no response to a napping question, or a frequency score where those who indicate napping more than one, two, or three times a week are distinguished as nappers compared to non-nappers who don’t meet these criteria. As the field lacks standard definitions for categorizing nap behavior, it is left to the discretion of the researcher to make these decisions. Furthermore, there is usually little other information collected about napping habits that could be used to better characterize napping behavior, such as lifetime nap habits, intentional vs accidental napping, and specific motivations for napping. These secondary factors have been shown to significantly moderate the effects of napping in experimental studies.
Considering the challenges, it is not surprising that there is wide disagreement across studies as to the health effects of napping.4 On the negative side, some studies have demonstrated that napping leads to increased risk of cardiovascular disease, dementia, and mortality.5-7 On the positive side, large cohort studies that control for some of these limitations report that habitual napping can predict better health outcomes, including lower mortality risk, reduced cardiovascular disease, and increased brain volume.8,9 Furthermore, age complicates matters as recent studies in older adults report that more frequent napping may be associated with reduced propensity for sleep during morning hours, and late afternoon naps were associated with earlier melatonin onset and increased evening activity, suggesting greater circadian misalignment in nappers and strategic use of napping as an evening fatigue countermeasure. More frequent napping in older adults was also correlated with lower cognitive performance in one of three cognitive domains. These results implicate more frequent and later-in-the-day napping habits in older adults may indicate altered circadian rhythms and reduced early morning sleep, with a potential functional impact on memory function. However, the same cautionary note applies to these studies, as few nap characteristics were reported that would help interpret the study outcomes and guide recommendations.10 Thus, the important and timely question of whether napping should be recommended does not, as of yet, have an answer. For clinicians weighing the multidimensional factors associated with napping in efforts to give a considered response to their patients, I can offer a set of questions that may help with tailoring responses to each individual. A lifetime history of napping can be an indicator of a health-promoting behavior, whereas a relatively recent desire to nap may reflect an underlying comorbidity that increases fatigue, sleepiness, and unintentional daytime sleep. Motivation for napping can also be revealing, as the desire to nap may be masking symptoms of depression and anxiety.11 Nighttime sleep disturbance may promote napping or, in some cases, arise from too much napping and should always be considered as a primary health measurement. In conclusion, it’s important to recognize the significance of addressing nighttime sleep disturbance and the potential impact of napping on overall health. For many, napping can be an essential and potent habit that can be encouraged throughout the lifespan for its salutary influences.
References
1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.
2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.
3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.
4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.
5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636
6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712
7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.
8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.
9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.
10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.
11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.
I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.
Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.
Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.
Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.
In the second context, epidemiological studies examining the impact of napping on health outcomes are typically conducted in older, less healthy, less active populations who tend to have poorer eating habits, multiple comorbidities, psychological problems, and a wide range of socioeconomic status. The strength of this approach is the sample size, which allows for correlations between factors on a large scale while providing enough data to hopefully control for possible confounds (eg, demographics, SES, exercise and eating habits, comorbidities). However, as the data were usually collected by a different group with different goals than the current epidemiologist exploring the data, there can be a disconnect between the current study goals and the variables that were initially collected by the original research team. As such, the current researcher is left with a patchwork of dissimilar variables that they must find a way to organize to answer the current question.3
When applied to the question of health effects of napping, epidemiology researchers typically divide the population into two groups, either based on a yes or no response to a napping question, or a frequency score where those who indicate napping more than one, two, or three times a week are distinguished as nappers compared to non-nappers who don’t meet these criteria. As the field lacks standard definitions for categorizing nap behavior, it is left to the discretion of the researcher to make these decisions. Furthermore, there is usually little other information collected about napping habits that could be used to better characterize napping behavior, such as lifetime nap habits, intentional vs accidental napping, and specific motivations for napping. These secondary factors have been shown to significantly moderate the effects of napping in experimental studies.
Considering the challenges, it is not surprising that there is wide disagreement across studies as to the health effects of napping.4 On the negative side, some studies have demonstrated that napping leads to increased risk of cardiovascular disease, dementia, and mortality.5-7 On the positive side, large cohort studies that control for some of these limitations report that habitual napping can predict better health outcomes, including lower mortality risk, reduced cardiovascular disease, and increased brain volume.8,9 Furthermore, age complicates matters as recent studies in older adults report that more frequent napping may be associated with reduced propensity for sleep during morning hours, and late afternoon naps were associated with earlier melatonin onset and increased evening activity, suggesting greater circadian misalignment in nappers and strategic use of napping as an evening fatigue countermeasure. More frequent napping in older adults was also correlated with lower cognitive performance in one of three cognitive domains. These results implicate more frequent and later-in-the-day napping habits in older adults may indicate altered circadian rhythms and reduced early morning sleep, with a potential functional impact on memory function. However, the same cautionary note applies to these studies, as few nap characteristics were reported that would help interpret the study outcomes and guide recommendations.10 Thus, the important and timely question of whether napping should be recommended does not, as of yet, have an answer. For clinicians weighing the multidimensional factors associated with napping in efforts to give a considered response to their patients, I can offer a set of questions that may help with tailoring responses to each individual. A lifetime history of napping can be an indicator of a health-promoting behavior, whereas a relatively recent desire to nap may reflect an underlying comorbidity that increases fatigue, sleepiness, and unintentional daytime sleep. Motivation for napping can also be revealing, as the desire to nap may be masking symptoms of depression and anxiety.11 Nighttime sleep disturbance may promote napping or, in some cases, arise from too much napping and should always be considered as a primary health measurement. In conclusion, it’s important to recognize the significance of addressing nighttime sleep disturbance and the potential impact of napping on overall health. For many, napping can be an essential and potent habit that can be encouraged throughout the lifespan for its salutary influences.
References
1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.
2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.
3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.
4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.
5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636
6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712
7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.
8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.
9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.
10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.
11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.
I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.
Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.
Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.
Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.
In the second context, epidemiological studies examining the impact of napping on health outcomes are typically conducted in older, less healthy, less active populations who tend to have poorer eating habits, multiple comorbidities, psychological problems, and a wide range of socioeconomic status. The strength of this approach is the sample size, which allows for correlations between factors on a large scale while providing enough data to hopefully control for possible confounds (eg, demographics, SES, exercise and eating habits, comorbidities). However, as the data were usually collected by a different group with different goals than the current epidemiologist exploring the data, there can be a disconnect between the current study goals and the variables that were initially collected by the original research team. As such, the current researcher is left with a patchwork of dissimilar variables that they must find a way to organize to answer the current question.3
When applied to the question of health effects of napping, epidemiology researchers typically divide the population into two groups, either based on a yes or no response to a napping question, or a frequency score where those who indicate napping more than one, two, or three times a week are distinguished as nappers compared to non-nappers who don’t meet these criteria. As the field lacks standard definitions for categorizing nap behavior, it is left to the discretion of the researcher to make these decisions. Furthermore, there is usually little other information collected about napping habits that could be used to better characterize napping behavior, such as lifetime nap habits, intentional vs accidental napping, and specific motivations for napping. These secondary factors have been shown to significantly moderate the effects of napping in experimental studies.
Considering the challenges, it is not surprising that there is wide disagreement across studies as to the health effects of napping.4 On the negative side, some studies have demonstrated that napping leads to increased risk of cardiovascular disease, dementia, and mortality.5-7 On the positive side, large cohort studies that control for some of these limitations report that habitual napping can predict better health outcomes, including lower mortality risk, reduced cardiovascular disease, and increased brain volume.8,9 Furthermore, age complicates matters as recent studies in older adults report that more frequent napping may be associated with reduced propensity for sleep during morning hours, and late afternoon naps were associated with earlier melatonin onset and increased evening activity, suggesting greater circadian misalignment in nappers and strategic use of napping as an evening fatigue countermeasure. More frequent napping in older adults was also correlated with lower cognitive performance in one of three cognitive domains. These results implicate more frequent and later-in-the-day napping habits in older adults may indicate altered circadian rhythms and reduced early morning sleep, with a potential functional impact on memory function. However, the same cautionary note applies to these studies, as few nap characteristics were reported that would help interpret the study outcomes and guide recommendations.10 Thus, the important and timely question of whether napping should be recommended does not, as of yet, have an answer. For clinicians weighing the multidimensional factors associated with napping in efforts to give a considered response to their patients, I can offer a set of questions that may help with tailoring responses to each individual. A lifetime history of napping can be an indicator of a health-promoting behavior, whereas a relatively recent desire to nap may reflect an underlying comorbidity that increases fatigue, sleepiness, and unintentional daytime sleep. Motivation for napping can also be revealing, as the desire to nap may be masking symptoms of depression and anxiety.11 Nighttime sleep disturbance may promote napping or, in some cases, arise from too much napping and should always be considered as a primary health measurement. In conclusion, it’s important to recognize the significance of addressing nighttime sleep disturbance and the potential impact of napping on overall health. For many, napping can be an essential and potent habit that can be encouraged throughout the lifespan for its salutary influences.
References
1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.
2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.
3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.
4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.
5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636
6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712
7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.
8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.
9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.
10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.
11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.
Exciting opportunities for tobacco treatment
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
Top reads from the CHEST journal portfolio
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Biomarker use in ARDS resulting from COVID-19 infection
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
Improved CHEST Physician® coming in 2025
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
Our Biggest Turnout Ever for Advocacy Day!
That’s why we gathered our leaders from across the United States in Washington, DC, to meet with congressional offices during our annual Advocacy Day.
GIs from California to Massachusetts and many states in between met with House and Senate offices to educate members of Congress and their staff about the most critical policy issues impacting you and your patients. In total, 28 states were represented and we attended more than 100 meetings in 64 different districts, which was a mix of both Republican and Democratic offices.
For the second year in a row, we were fortunate to be joined by GI patient advocates as well, who shared personal stories about the challenges they encountered in the health care system, and the negative effects to their well-being and quality of life because of red tape caused by prior authorization and step therapy.
The in-person advocacy of our members and patient advocates makes a difference. In one of AGA President Dr. Maria Abreu’s meetings, the congressional staffer remembered that he met with her, Dr. Mel Wilcox, and a patient advocate during 2023’s Advocacy Day and recounted the impact of their conversation about delays to timely access to care for inflammatory bowel disease medication.
Numerous GIs had similar experiences on Advocacy Day and recounted the benefits of being able to walk into House and Senate offices and educate congressional staff on the issues they’re experiencing in their clinic or lab.
Being able to start these conversations about health care and GI and build these relationships showcases the value of Advocacy Day, and demonstrates how AGA works with members to make it easy to advocate for the issues important to them. We were able to have a full day of constructive meetings with lawmakers and their staff thanks to members and patient advocates. Thank you for being engaged and using your voices to protect GI patient care!
That’s why we gathered our leaders from across the United States in Washington, DC, to meet with congressional offices during our annual Advocacy Day.
GIs from California to Massachusetts and many states in between met with House and Senate offices to educate members of Congress and their staff about the most critical policy issues impacting you and your patients. In total, 28 states were represented and we attended more than 100 meetings in 64 different districts, which was a mix of both Republican and Democratic offices.
For the second year in a row, we were fortunate to be joined by GI patient advocates as well, who shared personal stories about the challenges they encountered in the health care system, and the negative effects to their well-being and quality of life because of red tape caused by prior authorization and step therapy.
The in-person advocacy of our members and patient advocates makes a difference. In one of AGA President Dr. Maria Abreu’s meetings, the congressional staffer remembered that he met with her, Dr. Mel Wilcox, and a patient advocate during 2023’s Advocacy Day and recounted the impact of their conversation about delays to timely access to care for inflammatory bowel disease medication.
Numerous GIs had similar experiences on Advocacy Day and recounted the benefits of being able to walk into House and Senate offices and educate congressional staff on the issues they’re experiencing in their clinic or lab.
Being able to start these conversations about health care and GI and build these relationships showcases the value of Advocacy Day, and demonstrates how AGA works with members to make it easy to advocate for the issues important to them. We were able to have a full day of constructive meetings with lawmakers and their staff thanks to members and patient advocates. Thank you for being engaged and using your voices to protect GI patient care!
That’s why we gathered our leaders from across the United States in Washington, DC, to meet with congressional offices during our annual Advocacy Day.
GIs from California to Massachusetts and many states in between met with House and Senate offices to educate members of Congress and their staff about the most critical policy issues impacting you and your patients. In total, 28 states were represented and we attended more than 100 meetings in 64 different districts, which was a mix of both Republican and Democratic offices.
For the second year in a row, we were fortunate to be joined by GI patient advocates as well, who shared personal stories about the challenges they encountered in the health care system, and the negative effects to their well-being and quality of life because of red tape caused by prior authorization and step therapy.
The in-person advocacy of our members and patient advocates makes a difference. In one of AGA President Dr. Maria Abreu’s meetings, the congressional staffer remembered that he met with her, Dr. Mel Wilcox, and a patient advocate during 2023’s Advocacy Day and recounted the impact of their conversation about delays to timely access to care for inflammatory bowel disease medication.
Numerous GIs had similar experiences on Advocacy Day and recounted the benefits of being able to walk into House and Senate offices and educate congressional staff on the issues they’re experiencing in their clinic or lab.
Being able to start these conversations about health care and GI and build these relationships showcases the value of Advocacy Day, and demonstrates how AGA works with members to make it easy to advocate for the issues important to them. We were able to have a full day of constructive meetings with lawmakers and their staff thanks to members and patient advocates. Thank you for being engaged and using your voices to protect GI patient care!
An Investment in the Future of GI: The AGA Research Foundation
What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.
How will we get there? New treatments and devices are the result of years of research.
To help make this dream a reality, AGA — through the AGA Research Foundation — has made a commitment to support investigators in GI and hepatology with its Research Awards Program.
These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.
To our AGA Research Foundation donors, we sincerely thank you for your gifts.
We invite the GI community to join others in supporting and helping spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow.
Make your tax-deductible gift today at www.gastro.org/donateonline.
What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.
How will we get there? New treatments and devices are the result of years of research.
To help make this dream a reality, AGA — through the AGA Research Foundation — has made a commitment to support investigators in GI and hepatology with its Research Awards Program.
These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.
To our AGA Research Foundation donors, we sincerely thank you for your gifts.
We invite the GI community to join others in supporting and helping spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow.
Make your tax-deductible gift today at www.gastro.org/donateonline.
What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.
How will we get there? New treatments and devices are the result of years of research.
To help make this dream a reality, AGA — through the AGA Research Foundation — has made a commitment to support investigators in GI and hepatology with its Research Awards Program.
These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.
To our AGA Research Foundation donors, we sincerely thank you for your gifts.
We invite the GI community to join others in supporting and helping spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow.
Make your tax-deductible gift today at www.gastro.org/donateonline.
Gastro Journal Club: Proximal Cancers in FIT-Positive Patients
For our next installment of the Gastro Journal Club, They are joined by fellows from the Icahn School of Medicine at Mount Sinai in New York City for a discussion of the article “Risk of Cancers Proximal to the Colon in Fecal Immunochemical Test Positive Screenees in a Colorectal Cancer Screening Program,” published in the September 2024 issue of Gastroenterology .
Visit our YouTube Channel (youtube.com/@AmerGastroAssn) to watch the session.
The Gastro Journal Club is by and for fellows and residents. During these sessions, fellows and residents have the opportunity to ask authors questions about their recently published work in Gastroenterology. If you are interested in arranging a Gastro Journal Club session at your institution, please contact [email protected].
For our next installment of the Gastro Journal Club, They are joined by fellows from the Icahn School of Medicine at Mount Sinai in New York City for a discussion of the article “Risk of Cancers Proximal to the Colon in Fecal Immunochemical Test Positive Screenees in a Colorectal Cancer Screening Program,” published in the September 2024 issue of Gastroenterology .
Visit our YouTube Channel (youtube.com/@AmerGastroAssn) to watch the session.
The Gastro Journal Club is by and for fellows and residents. During these sessions, fellows and residents have the opportunity to ask authors questions about their recently published work in Gastroenterology. If you are interested in arranging a Gastro Journal Club session at your institution, please contact [email protected].
For our next installment of the Gastro Journal Club, They are joined by fellows from the Icahn School of Medicine at Mount Sinai in New York City for a discussion of the article “Risk of Cancers Proximal to the Colon in Fecal Immunochemical Test Positive Screenees in a Colorectal Cancer Screening Program,” published in the September 2024 issue of Gastroenterology .
Visit our YouTube Channel (youtube.com/@AmerGastroAssn) to watch the session.
The Gastro Journal Club is by and for fellows and residents. During these sessions, fellows and residents have the opportunity to ask authors questions about their recently published work in Gastroenterology. If you are interested in arranging a Gastro Journal Club session at your institution, please contact [email protected].
Top reads from the CHEST journal portfolio
Explore articles on PAP adherence, plasma biomarkers in ARDS, and airways disorders hospitalizations during wildfire season
Journal CHEST®
Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA
By Launois, MD, PhD, and colleagues
One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.
This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.
– Commentary by Sai Venkateshiah, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies
By Alladina, MD, and colleagues
Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.
– Commentary by Daniel R. Ouellette, MD, FCCP, Critical Care Commentary Editor of CHEST Physician
CHEST® Pulmonary
Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods
By Horne, PhD, MStat, MPH, and colleagues
Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.
– Commentary by Diego J. Maselli, MD, FCCP, Member of the CHEST Physician Editorial Board
Explore articles on PAP adherence, plasma biomarkers in ARDS, and airways disorders hospitalizations during wildfire season
Explore articles on PAP adherence, plasma biomarkers in ARDS, and airways disorders hospitalizations during wildfire season
Journal CHEST®
Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA
By Launois, MD, PhD, and colleagues
One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.
This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.
– Commentary by Sai Venkateshiah, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies
By Alladina, MD, and colleagues
Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.
– Commentary by Daniel R. Ouellette, MD, FCCP, Critical Care Commentary Editor of CHEST Physician
CHEST® Pulmonary
Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods
By Horne, PhD, MStat, MPH, and colleagues
Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.
– Commentary by Diego J. Maselli, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA
By Launois, MD, PhD, and colleagues
One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.
This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.
– Commentary by Sai Venkateshiah, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies
By Alladina, MD, and colleagues
Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.
– Commentary by Daniel R. Ouellette, MD, FCCP, Critical Care Commentary Editor of CHEST Physician
CHEST® Pulmonary
Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods
By Horne, PhD, MStat, MPH, and colleagues
Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.
– Commentary by Diego J. Maselli, MD, FCCP, Member of the CHEST Physician Editorial Board