Manuela Callari

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

 

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

 

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.■

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.■

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

In 2016, Brady Scott was in his parents’ home in Garrett, Kentucky, scrolling his Facebook feed when a post from a local newspaper caught his attention. “The article said that if you grew up in the region I grew up in, compared to the richer Central Kentucky region, the life expectancy differed by about 9 years,” he recalled.

The respiratory therapist, then a PhD student at Rush University, Chicago, was struck and began “Googling” to find out why this was the case. Initially, he thought diabetes, smoking, and economic distress — all prevalent problems in the area — were the culprits. However, he soon found that respiratory disease was particularly common in his region.

Now a professor and program director of the Respiratory Care Program at Rush University, Scott has spent several years trying to understand why people in certain regions experience respiratory illness at higher rates than in other places.

The Environment as a Determinant of Health

When Scott began his PhD, the prevalence of asthma in Southeast Kentucky, part of the Appalachian region, was already well-documented. He focused his research on uncontrolled asthma and the triggers that drove asthma exacerbations.

Housing quality emerged as an important factor. He found that exposure to mold, mildew, dust mites, pests, and rodents increased the risk for asthma and exacerbated existing cases. Lower-income families, more likely to live in poor-quality housing, were significantly affected, even in single-family homes.

Wanda Phipatanakul, MD, MS, director of the Division of Immunology Research Center at Boston Children’s Hospital and S. Jean Emans professor of Pediatrics at Harvard Medical School, Boston, has found similar results in urban environments. She said cockroach and mouse allergen exposure is disproportionately prevalent in urban, low-income neighborhoods. These exposures, closely tied to housing conditions, contribute to worse asthma and respiratory problems, particularly in children.

Scott and Phipatanakul agreed that the environment surrounding people’s homes can also exacerbate respiratory disease.

Rural areas present unique risks, such as agricultural activities that release pesticides and other particulates into the air, said Scott. In mountainous areas like Appalachia, mining operations are another significant contributor. For example, blasting mountains with dynamite creates large clouds of dust and pollutants that settle in valleys. Coal-hauling roads contribute to air quality issues, too. And houses near these roads may be exposed to increased levels of particulate matter, he said.

In the city, Phipatanakul has found that historical practices like redlining have systematically denied certain neighborhoods access to resources and investment, leaving a legacy of poor infrastructure, limited resources, and higher exposure to environmental risks. Today, these areas have more highways and fewer green spaces and are disproportionately linked with a higher incidence of respiratory illnesses.

The findings of both Scott and Phipatanakul underscore a critical bottom line: Health disparities are deeply influenced by environmental factors, which are themselves shaped by socioeconomic conditions and historical inequities. Poor housing quality, exposure to allergens, and proximity to environmental hazards disproportionately affect underserved and minority communities, whether in rural or urban settings.

The Role of Green Spaces in Improving Respiratory Health

Restoring and increasing tree cover and green spaces in urban areas can significantly improve respiratory health by addressing environmental challenges and reducing triggers for respiratory issues. Areas with greater greenness tend to have lower levels of pollutants and fewer environmental infestations, such as mice and cockroaches, explained Phipatanakul. Her research highlights that schools in greener areas have fewer airborne pollutants and particles than those in more urbanized, less green areas, which are usually in poorer suburbs.

Trees absorb pollutants such as particulate matter and sulfur dioxide through dry deposition and stomatal uptake, improving air quality. “The question is whether we can use trees as a public health tool, and this is being done in many cities,” said Alessandro Marcon, PhD, a professor of epidemiology and medical statistics at the University of Verona, Verona, Italy, while speaking at the European Respiratory Society conference held in Vienna last September.

A US analysis showed that existing natural vegetation, such as forests and grasslands, absorbs a large portion of emissions. By restoring land cover, pollution from harmful substances like sulfur dioxide and particulate matter could be reduced by about 30%. This approach is often more cost-effective than technological solutions for managing emissions.

Moreover, tree cover contributes to a healthier air microbiome. Research indicates that urban forest areas have lower pathogenic bacteria and fungi concentrations than nearby urban zones.

Another major advantage is the mitigation of the urban heat island effect. A study conducted in Paris found that municipalities with higher tree coverage experienced 20%-30% lower heat-related mortality than those with less greenery. Increasing tree coverage to 30% could reduce up to 40% of excess mortality associated with urban heat islands. Trees achieve this by providing shade and facilitating evapotranspiration, which cools the surrounding air.

Urban environments, unsurprisingly, often have higher levels of air pollution due to increased traffic and industrial activity. However, despite appearing greener, rural environments may harbor less obvious but significant sources of air pollution. “I live in an urban environment now, but I grew up in a rural environment,” Scott said. “Each has its own issues that affect air quality and health.”

Scott, Phipatanakul, and Marcon reported no relevant financial relationships.■

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

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.

XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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