Immunology

From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.

To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.

What is the role of the gut barrier in overall health and disease?

The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.

The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.

Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.



Is disruption of this barrier what is usually referred to as “leaky gut”?

Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.



Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?

Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.

In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.

In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
 

The many possible sources of gut-barrier disruption

What causes leaky gut, and when should physicians and patients be suspicious if they have it?

There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO₂ max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.

Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.



What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?

The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.

With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.

A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
 

Emerging evidence on causality

New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?

Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.

Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.

In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.

In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.

These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.



What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?

There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.



Is there an association between alterations in the gut microbiome and gut-barrier disruption?

There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.

The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.

Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
 

Practical advice for clinicians and patients

How do you advise patients to avoid gut-barrier disruption?

It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.

Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?

Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.

Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.

What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?

It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
 

Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.

A version of this article appeared on Medscape.com.

From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.

To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.

What is the role of the gut barrier in overall health and disease?

The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.

The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.

Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.



Is disruption of this barrier what is usually referred to as “leaky gut”?

Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.



Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?

Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.

In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.

In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
 

The many possible sources of gut-barrier disruption

What causes leaky gut, and when should physicians and patients be suspicious if they have it?

There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO₂ max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.

Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.



What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?

The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.

With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.

A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
 

Emerging evidence on causality

New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?

Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.

Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.

In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.

In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.

These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.



What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?

There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.



Is there an association between alterations in the gut microbiome and gut-barrier disruption?

There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.

The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.

Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
 

Practical advice for clinicians and patients

How do you advise patients to avoid gut-barrier disruption?

It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.

Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?

Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.

Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.

What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?

It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
 

Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.

A version of this article appeared on Medscape.com.

From Ayurveda to the teachings of Hippocrates, medicine’s earliest traditions advanced a belief that the gut was the foundation of all health and disease. It wasn’t until recently, however, that Western medicine has adopted the notion of gut-barrier dysfunction as a pathologic phenomenon critical to not only digestive health but also chronic allergic, inflammatory, and autoimmune disease.

To learn more, Medscape contributor Akash Goel, MD, interviewed Elena Ivanina, DO, MPH, an integrative gastroenterologist, on the role of the gut barrier. Dr. Ivanina is the founder of the Center for Integrative Gut Health and the former director of Neurogastroenterology and Motility at Lenox Hill Hospital in New York. She runs the educational platform for all things gut health, gutlove.com.

What is the role of the gut barrier in overall health and disease?

The gut contains the human body’s largest interface between a person and their external environment. The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins.

The gut barrier is made up of the mucus layer, gut microbiome, epithelial cells, and immune cells in the lamina propria. When this apparatus is disrupted by factors such as infection, low-fiber diet, antibiotics, and alcohol, then it cannot function normally to selectively keep out the harmful intraluminal substances.

Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. This causes improper immune activation and dysregulation, which has been shown to lead to various diseases, including gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) and celiac disease, systemic autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and metabolic diseases such as obesity and diabetes.



Is disruption of this barrier what is usually referred to as “leaky gut”?

Leaky gut is a colloquial term for increased intestinal permeability or intestinal hyperpermeability. In a 2019 review article, Dr. Michael Camilleri exposes leaky gut as a term that can be misleading and confusing to the general population. It calls upon clinicians to have an increased awareness of the potential of barrier dysfunction in diseases, and to consider the barrier as a target for treatment.



Is leaky gut more of a mechanism of underlying chronic disease or is it a disease of its own?

Intestinal permeability is a pathophysiologic process in the gut with certain risk factors that in some conditions has been shown to precede chronic disease. There has not been any convincing evidence that it can be diagnosed and treated as its own entity, but research is ongoing.

In IBD, the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project research consortium has been studying individuals at increased risk for Crohn’s disease because of a first-degree family member with Crohn’s disease. They found an increased abundance of Ruminococcus torques in the microbiomes of at-risk individuals who went on to develop the disease. R. torques are mucin degraders that induce an increase in other mucin-using bacteria, which can contribute to gut-barrier compromise.

In other studies, patients have been found to have asymptomatic intestinal hyperpermeability years before their diagnosis of Crohn’s disease. This supports understanding more about the potential of intestinal hyperpermeability as its own diagnosis that, if addressed, could possibly prevent disease development.
 

The many possible sources of gut-barrier disruption

What causes leaky gut, and when should physicians and patients be suspicious if they have it?

There are many risk factors that have been associated with leaky gut in both human studies and animal studies, including acrolein (food toxin), aging, alcohol, antacid drugs, antibiotics, burn injury, chemotherapy, circadian rhythm disruption, corticosteroids, emulsifiers (food additives), strenuous exercise (≥ 2 hours) at 60% VO₂ max, starvation, fructose, fructans, gliadin (wheat protein), high-fat diet, high-salt diet, high-sugar diet, hyperglycemia, low-fiber diet, nonsteroidal anti-inflammatory drugs, pesticide, proinflammatory cytokines, psychological stress, radiation, sleep deprivation, smoking, and sweeteners.

Patients may be completely asymptomatic with leaky gut. Physicians should be suspicious if there is a genetic predisposition to chronic disease or if any risk factors are unveiled after assessing diet and lifestyle exposures.



What is the role of the Western diet and processed food consumption in driving disruptions of the gut barrier?

The Western diet reduces gut-barrier mucus thickness, leading to increased gut permeability. People who consume a Western diet typically eat less than 15 grams of fiber per day, which is significantly less than many other cultures, including the hunter-gatherers of Tanzania (Hadza), who get 100 or more grams of fiber a day in their food.

With a fiber-depleted diet, gut microbiota that normally feed on fiber gradually disappear and other commensals shift their metabolism to degrade the gut-barrier mucus layer.

A low-fiber diet also decreases short-chain fatty acid production, which reduces production of mucus and affects tight junction regulation.
 

Emerging evidence on causality

New evidence is demonstrating that previous functional conditions of the gastrointestinal tract, like functional dyspepsia, are associated with abnormalities to the intestinal barrier. What is the association between conditions like functional dyspepsia and irritable bowel syndrome (IBS) with gut-barrier disruption?

Conditions such as functional dyspepsia and IBS are similar in that their pathophysiology is incompletely understood and likely attributable to contributions from many different underlying mechanisms. This makes it difficult for clinicians to explain the condition to patients and often to treat without specific therapeutic targets.

Emerging evidence with new diagnostic tools, such as confocal laser endomicroscopy, has demonstrated altered mucosal barrier function in both conditions.

In patients with IBS who have a suspected food intolerance, studies looking at exposure to the food antigens found that the food caused immediate breaks, increased intervillous spaces, and increased inflammatory cells in the gut mucosa. These changes were associated with patient responses to exclusion diets.

In functional dyspepsia, another study, using confocal laser endomicroscopy, has shown that affected patients have significantly greater epithelial gap density in the duodenum, compared with healthy controls. There was also impaired duodenal-epithelial barrier integrity and evidence of increased cellular pyroptosis in the duodenal mucosa.

These findings suggest that while IBS and functional dyspepsia are still likely multifactorial, there may be a common preclinical state that can be further investigated as far as preventing its development and using it as a therapeutic target.



What diagnostic testing are you using to determine whether patients have disruptions to the gut barrier? Are they validated or more experimental?

There are various testing strategies that have been used in research to diagnose intestinal hyperpermeability. In a 2021 analysis, Dr. Michael Camilleri found that the optimal probes for measuring small intestinal and colonic permeability are the mass excreted of 13C-mannitol at 0-2 hours and lactulose during 2-8 hours or sucralose during 8-24 hours. Studies looking at postinfectious IBS have incorporated elevated urinary lactulose/mannitol ratios. Dr. Alessio Fasano and others have looked at using zonulin as a biomarker of impaired gut-barrier function. These tests are still considered experimental.



Is there an association between alterations in the gut microbiome and gut-barrier disruption?

There is an integral relationship between the gut microbiome and gut-barrier function, and dysbiosis can disrupt gut-barrier functionality.

The microbiota produce a variety of metabolites in close proximity to the gut epithelium, impacting gut-barrier function and immune response. For example, short-chain fatty acids produced by Bifidobacterium, Bacteroides, Enterobacter, Faecalibacterium, and Roseburia species impact host immune cell differentiation and metabolism as well as influence susceptibility to pathogens.

Studies have shown that sodium butyrate significantly improves epithelial-barrier function. Other experiments have used transplantation of the intestinal microbiota to show that introduction of certain microbial phenotypes can significantly increase gut permeability.
 

Practical advice for clinicians and patients

How do you advise patients to avoid gut-barrier disruption?

It is important to educate and counsel patients about the long list of risk factors, many of which are closely related to a Western diet and lifestyle, which can increase their risk for leaky gut.

Once one has it, can it be repaired? Can you share a bit about your protocols in general terms?

Many interventions have been shown to improve intestinal permeability. They include berberine, butyrate, caloric restriction and fasting, curcumin, dietary fiber (prebiotics), moderate exercise, fermented food, fish oil, glutamine, quercetin, probiotics, vagus nerve stimulation, vitamin D, and zinc.

Protocols have to be tailored to patients and their risk factors, diet, and lifestyle.

What are some tips from a nutrition and lifestyle standpoint that patients can follow to ensure a robust gut barrier?

It is important to emphasize a high-fiber diet with naturally fermented food, incorporating time-restricted eating, such as eating an early dinner and nothing else before bedtime, a moderate exercise routine, and gut-brain modulation with techniques such as acupuncture that can incorporate vagus nerve stimulation. Limited safe precision supplementation can be discussed on an individual basis based on the patient’s interest, additional testing, and other existing health conditions.
 

Dr. Akash Goel is a clinical assistant professor of medicine at Weill Cornell in gastroenterology and hepatology. He has disclosed no relevant financial relationships. His work has appeared on networks and publications such as CNN, The New York Times, Time Magazine, and Financial Times. He has a deep interest in nutrition, food as medicine, and the intersection between the gut microbiome and human health.

A version of this article appeared on Medscape.com.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the biologic tezepelumab (Tezspire, Amgen) had similar efficacy at reducing exacerbations, improving lung function, and symptom control as observed in patients with asthma alone, according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.

GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.

The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.

Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.

Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.

TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.

The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).

Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).

There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).

The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.

The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.

Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the biologic tezepelumab (Tezspire, Amgen) had similar efficacy at reducing exacerbations, improving lung function, and symptom control as observed in patients with asthma alone, according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.

GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.

The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.

Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.

Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.

TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.

The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).

Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).

There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).

The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.

The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.

Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the biologic tezepelumab (Tezspire, Amgen) had similar efficacy at reducing exacerbations, improving lung function, and symptom control as observed in patients with asthma alone, according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.

GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.

The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.

Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.

Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.

TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.

The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).

Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).

There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).

The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.

The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.

“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.

Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.

She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.

During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.

The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
 

Key outcomes

At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).

At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.

The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:

• EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
• EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
• Change in body weight for age percentile (+3.09 vs. +0.29).
• Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).

At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.

The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
 

‘Good safety profile’

Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.

“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”

“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”

The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Half of kids with COVID-19 become noninfectious 3 days after testing positive, whether they were vaccinated or not, according to a new study. The findings indicate that return-to-school policies for infected children may not need to differ on the basis of vaccine or booster status.

METHODOLOGY:

• The study looked at 76 children, both vaccinated and unvaccinated, aged 7-18 years who had tested positive for COVID-19. 
• Researchers performed nasal swabs every other day for 10 days, sending the swab to a lab to be tested for cytopathic effect (CPE), or cell death, an indicator of infectivity.
• They took pictures of the lab cultures to look for signs of CPE starting at 6 days after the test, which corresponds to the 2nd day after testing positive.
• If CPE characteristics were present in at least 30% of images, children were considered infectious.

TAKEAWAY:

• By day 3, half of study participants were noninfectious, independent of whether they had been vaccinated.
• By day 5, less than 25% of children were infectious, regardless of vaccination status.
• Among vaccinated children, the duration of infectivity was similar for children who received a booster and for those who had not.
• The authors state that these results are consistent with those of a study in adults with the Omicron variant, which found no association between vaccination status and infectivity duration.

IN PRACTICE:

“Our findings suggest that current policies requiring isolation for 5 days after a positive test might be appropriate, as the majority of children were not infectious by day 5. Additionally, return-to-school policies may not need to discriminate by vaccine or booster status,” the authors wrote. 

SOURCE:

The study was led by Neeraj Sood, PhD, of the University of Southern California in Los Angeles, and was published in JAMA Pediatrics.

LIMITATIONS:

The sample size was small, and the authors identified the potential for nonresponse bias. The research did not include data from children who didn’t receive a test. CPE is the standard for estimating infectivity, but it can still carry inaccuracies.

DISCLOSURES:

The authors report no disclosures. The study was funded by RF Catalytic Capital.

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

TOPLINE:

Half of kids with COVID-19 become noninfectious 3 days after testing positive, whether they were vaccinated or not, according to a new study. The findings indicate that return-to-school policies for infected children may not need to differ on the basis of vaccine or booster status.

METHODOLOGY:

• The study looked at 76 children, both vaccinated and unvaccinated, aged 7-18 years who had tested positive for COVID-19. 
• Researchers performed nasal swabs every other day for 10 days, sending the swab to a lab to be tested for cytopathic effect (CPE), or cell death, an indicator of infectivity.
• They took pictures of the lab cultures to look for signs of CPE starting at 6 days after the test, which corresponds to the 2nd day after testing positive.
• If CPE characteristics were present in at least 30% of images, children were considered infectious.

TAKEAWAY:

• By day 3, half of study participants were noninfectious, independent of whether they had been vaccinated.
• By day 5, less than 25% of children were infectious, regardless of vaccination status.
• Among vaccinated children, the duration of infectivity was similar for children who received a booster and for those who had not.
• The authors state that these results are consistent with those of a study in adults with the Omicron variant, which found no association between vaccination status and infectivity duration.

IN PRACTICE:

“Our findings suggest that current policies requiring isolation for 5 days after a positive test might be appropriate, as the majority of children were not infectious by day 5. Additionally, return-to-school policies may not need to discriminate by vaccine or booster status,” the authors wrote. 

SOURCE:

The study was led by Neeraj Sood, PhD, of the University of Southern California in Los Angeles, and was published in JAMA Pediatrics.

LIMITATIONS:

The sample size was small, and the authors identified the potential for nonresponse bias. The research did not include data from children who didn’t receive a test. CPE is the standard for estimating infectivity, but it can still carry inaccuracies.

DISCLOSURES:

The authors report no disclosures. The study was funded by RF Catalytic Capital.

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

TOPLINE:

Half of kids with COVID-19 become noninfectious 3 days after testing positive, whether they were vaccinated or not, according to a new study. The findings indicate that return-to-school policies for infected children may not need to differ on the basis of vaccine or booster status.

METHODOLOGY:

• The study looked at 76 children, both vaccinated and unvaccinated, aged 7-18 years who had tested positive for COVID-19. 
• Researchers performed nasal swabs every other day for 10 days, sending the swab to a lab to be tested for cytopathic effect (CPE), or cell death, an indicator of infectivity.
• They took pictures of the lab cultures to look for signs of CPE starting at 6 days after the test, which corresponds to the 2nd day after testing positive.
• If CPE characteristics were present in at least 30% of images, children were considered infectious.

TAKEAWAY:

• By day 3, half of study participants were noninfectious, independent of whether they had been vaccinated.
• By day 5, less than 25% of children were infectious, regardless of vaccination status.
• Among vaccinated children, the duration of infectivity was similar for children who received a booster and for those who had not.
• The authors state that these results are consistent with those of a study in adults with the Omicron variant, which found no association between vaccination status and infectivity duration.

IN PRACTICE:

“Our findings suggest that current policies requiring isolation for 5 days after a positive test might be appropriate, as the majority of children were not infectious by day 5. Additionally, return-to-school policies may not need to discriminate by vaccine or booster status,” the authors wrote. 

SOURCE:

The study was led by Neeraj Sood, PhD, of the University of Southern California in Los Angeles, and was published in JAMA Pediatrics.

LIMITATIONS:

The sample size was small, and the authors identified the potential for nonresponse bias. The research did not include data from children who didn’t receive a test. CPE is the standard for estimating infectivity, but it can still carry inaccuracies.

DISCLOSURES:

The authors report no disclosures. The study was funded by RF Catalytic Capital.

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

The U.S. Food and Drug Administration has approved a meningococcal vaccine against the five most common serogroups causing disease in children and young adults.

The new formulation called Penbraya is manufactured by Pfizer and combines the components from two existing meningococcal vaccines, Trumenba the group B vaccine and Nimenrix groups A, C, W-135, and Y conjugate vaccine.

This is the first pentavalent vaccine for meningococcal disease and is approved for use in people aged 10-25.

“Today marks an important step forward in the prevention of meningococcal disease in the U.S.,” Annaliesa Anderson, PhD, head of vaccine research and development at Pfizer, said in a news release. “In a single vaccine, Penbraya has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”
 

One shot, five common types

“Incomplete protection against invasive meningococcal disease,” is common, added Jana Shaw, MD, MPH, a pediatric infectious diseases specialist from Upstate Golisano Children’s Hospital in Syracuse, N.Y. Reducing the number of shots is important because streamlining the vaccination process should help increase the number of young people who get fully vaccinated against meningococcal disease.

Rates are low in the United States, according to the Centers for Disease Control and Prevention, and in 2021 there were around 210 cases reported. But a statewide outbreak has been going on in Virginia since June 2022, with 29 confirmed cases and 6 deaths.

The FDA’s decision is based on the positive results from phase 2 and phase 3 trials, including a randomized, active-controlled and observer-blinded phase 3 trial assessing the safety, tolerability, and immunogenicity of the pentavalent vaccine candidate, compared with currently licensed meningococcal vaccines. The phase 3 trial evaluated more than 2,400 patients from the United States and Europe.

The CDC Advisory Committee on Immunization Practices is meeting on Oct. 25 to discuss recommendations for the appropriate use of Penbraya in young people.

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

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having no relevant financial relationships.

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

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having no relevant financial relationships.

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

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having no relevant financial relationships.

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

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

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

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

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

The newly approved respiratory syncytial virus vaccine administered during pregnancy substantially reduces the clinical and economic burden of lower respiratory tract disease caused by RSV, according to research presented at an annual scientific meeting on infectious diseases.

“With RSV maternal vaccination that is associated with clinical efficacy of 69% against severe RSV disease at 6 months, we estimated that up to 200,000 cases can be averted, and that is associated with almost $800 million in total,” presenting author Amy W. Law, PharmD, director of global value and evidence at Pfizer, pointed out during a news briefing.

“RSV is associated with a significant burden in the U.S. and this newly approved and recommended maternal RSV vaccine can have substantial impact in easing some of that burden,” Dr. Law explained.

This study is “particularly timely as we head into RSV peak season,” said briefing moderator Natasha Halasa, MD, MPH, professor of pediatrics, division of pediatric infectious diseases at Vanderbilt University, Nashville, Tenn.

The challenge, said Dr. Halasa, is that uptake of maternal vaccines and vaccines in general is “not optimal,” making increased awareness of this new maternal RSV vaccine important.
 

Strong efficacy data

Most children are infected with RSV at least once by the time they reach age 2 years. Very young children are at particular risk of severe complications, such as pneumonia or bronchitis.

As reported previously by this news organization, in the randomized, double-blind, placebo-controlled phase 3 study, Pfizer’s maternal RSV vaccine had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. As part of the trial, a total of 7,400 women received a single dose of the vaccine in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Based on the results, the U.S. Food and Drug Administration approved the vaccine, known as Abrysvo, in August, to be given between weeks 32 and 36 of pregnancy.
 

New modeling study

Dr. Law and colleagues modeled the potential public health impact – both clinical and economic – of the maternal RSV vaccine among the population of all pregnant women and their infants born during a 12-month period in the United States. The model focused on severe RSV disease in babies that required medical attention.

According to their model, without widespread use of the maternal RSV vaccine, 48,246 hospitalizations, 144,495 emergency department encounters, and 399,313 outpatient clinic visits related to RSV are projected to occur annually among the U.S. birth cohort of 3.7 million infants younger than 12 months.

With widespread use of the vaccine, annual hospitalizations resulting from infant RSV would fall by 51%, emergency department encounters would decline by 32%, and outpatient clinic visits by 32% – corresponding to a decrease in direct medical costs of about $692 million and indirect nonmedical costs of roughly $110 million.

Dr. Law highlighted two important caveats to the data. “The protections are based on the year-round administration of the vaccine to pregnant women at 32 to 36 weeks’ gestational age, and this is also assuming 100% uptake. Of course, in reality, that most likely is not the case,” she told the briefing.

Dr. Halasa noted that the peak age for severe RSV illness is 3 months and it’s tough to identify infants at highest risk for severe RSV.

Nearly 80% of infants with RSV who are hospitalized do not have an underlying medical condition, “so we don’t even know who those high-risk infants are. That’s why having this vaccine is so exciting,” she told the briefing.

Dr. Halasa said it’s also important to note that infants with severe RSV typically make not just one but multiple visits to the clinic or emergency department, leading to missed days of work for the parent, not to mention the “emotional burden of having your otherwise healthy newborn or young infant in the hospital.”

In addition to Pfizer’s maternal RSV vaccine, the FDA in July approved AstraZeneca’s monoclonal antibody nirsevimab (Beyfortus) for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.

The study was funded by Pfizer. Dr. Law is employed by Pfizer. Dr. Halasa has received grant and research support from Merck.

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