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Could a Fungal Infection Cause a Future Pandemic?
The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking.
The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.
What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.
Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?
We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.
“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.
Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.
“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.
The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.
In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.
“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.
In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.
In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.
“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
Need for More Medical Mycology Training
Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.
“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.
For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.
“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.
He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”
Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.
“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.
More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.
“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.
According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.
But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.
This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.
In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.
Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
Why Are Resistant Fungal Infections Becoming Increasingly Common?
The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body.
“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.
However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”
It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.
But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.
Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.
It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.
Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.
This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.
Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
One Health in Fungal Infections
The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.
“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.
According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.
“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.
Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.
Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.
“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.
She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.
“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.
Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
Alarms Sound for Candida auris
The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.
“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.
Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.
Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.
As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.
In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.
However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
Open Ending
As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.
But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.
“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.
At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.
“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.
He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.
Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.
Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?
Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest.
This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking.
The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.
What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.
Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?
We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.
“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.
Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.
“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.
The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.
In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.
“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.
In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.
In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.
“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
Need for More Medical Mycology Training
Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.
“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.
For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.
“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.
He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”
Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.
“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.
More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.
“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.
According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.
But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.
This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.
In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.
Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
Why Are Resistant Fungal Infections Becoming Increasingly Common?
The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body.
“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.
However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”
It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.
But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.
Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.
It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.
Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.
This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.
Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
One Health in Fungal Infections
The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.
“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.
According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.
“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.
Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.
Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.
“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.
She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.
“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.
Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
Alarms Sound for Candida auris
The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.
“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.
Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.
Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.
As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.
In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.
However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
Open Ending
As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.
But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.
“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.
At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.
“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.
He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.
Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.
Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?
Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest.
This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking.
The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.
What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.
Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?
We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.
“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.
Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.
“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.
The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.
In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.
“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.
In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.
In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.
“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
Need for More Medical Mycology Training
Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.
“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.
For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.
“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.
He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”
Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.
“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.
More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.
“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.
According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.
But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.
This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.
In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.
Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
Why Are Resistant Fungal Infections Becoming Increasingly Common?
The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body.
“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.
However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”
It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.
But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.
Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.
It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.
Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.
This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.
Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
One Health in Fungal Infections
The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.
“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.
According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.
“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.
Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.
Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.
“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.
She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.
“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.
Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
Alarms Sound for Candida auris
The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.
“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.
Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.
Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.
As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.
In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.
However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
Open Ending
As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.
But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.
“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.
At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.
“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.
He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.
Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.
Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?
Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest.
This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Machine learning meets cardiopulmonary exercise testing
DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK
Pulmonary Physiology and Rehabilitation Section
Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.1
Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.2 Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.
A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO2 peak and FEV1 alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.
Overall, these results suggest that refinement of machine learning algorithms built with larger heterogeneous data sets and expert interpretation can make CPETs accessible to the nonexpert clinician as long as test quality can be replicated across centers.
–Joseph Russo, MD
Fellow-in-Training
– Fatima Zeba, MD
Member-at-Large
References
1. Portella JJ, Andonian BJ, Brown DE, et al. Using machine learning to identify organ system specific limitations to exercise via cardiopulmonary exercise testing. IEEE J Biomed Health Inform. 2022;26(8):4228-4237.
2. Schwendinger F, Biehler AK, Nagy-Huber M, et al. Using machine learning-based algorithms to identify and quantify exercise limitations in clinical practice: are we there yet? Med Sci Sports Exerc. 2024;56(2):159-169.
DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK
Pulmonary Physiology and Rehabilitation Section
Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.1
Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.2 Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.
A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO2 peak and FEV1 alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.
Overall, these results suggest that refinement of machine learning algorithms built with larger heterogeneous data sets and expert interpretation can make CPETs accessible to the nonexpert clinician as long as test quality can be replicated across centers.
–Joseph Russo, MD
Fellow-in-Training
– Fatima Zeba, MD
Member-at-Large
References
1. Portella JJ, Andonian BJ, Brown DE, et al. Using machine learning to identify organ system specific limitations to exercise via cardiopulmonary exercise testing. IEEE J Biomed Health Inform. 2022;26(8):4228-4237.
2. Schwendinger F, Biehler AK, Nagy-Huber M, et al. Using machine learning-based algorithms to identify and quantify exercise limitations in clinical practice: are we there yet? Med Sci Sports Exerc. 2024;56(2):159-169.
DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK
Pulmonary Physiology and Rehabilitation Section
Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.1
Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.2 Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.
A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO2 peak and FEV1 alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.
Overall, these results suggest that refinement of machine learning algorithms built with larger heterogeneous data sets and expert interpretation can make CPETs accessible to the nonexpert clinician as long as test quality can be replicated across centers.
–Joseph Russo, MD
Fellow-in-Training
– Fatima Zeba, MD
Member-at-Large
References
1. Portella JJ, Andonian BJ, Brown DE, et al. Using machine learning to identify organ system specific limitations to exercise via cardiopulmonary exercise testing. IEEE J Biomed Health Inform. 2022;26(8):4228-4237.
2. Schwendinger F, Biehler AK, Nagy-Huber M, et al. Using machine learning-based algorithms to identify and quantify exercise limitations in clinical practice: are we there yet? Med Sci Sports Exerc. 2024;56(2):159-169.
Pulmonary telerehabilitation for COPD: Promising, but more data needed
As COVID-19 cedes its pandemic-scale status to the past, its wake is revealing surprises and raising questions, particularly in relation to pulmonary medicine. The need for isolation at COVID’s outset kept many millions at home, creating conditions favorable for the rapid expansion of technologies that were taken up quickly in telehealth applications. The need was overwhelming. But just how effective telehealth actually is at replacing on-site programs for COPD pulmonary rehab has remained a research challenge, although results from early studies show unmistakable value. Creating conditions conducive to research into the strengths and weaknesses of pulmonary rehab, and determining how research can be applied effectively, remain formidable challenges.
Early studies of telehealth pulmonary rehabilitation have not uncovered any glaring erosion of pulmonary rehabilitation’s well-established benefits. But, at the same time, the relatively young field of pulmonary telerehabilitation for chronic obstructive pulmonary disease (COPD) has lacked coordinated efforts to determine its key practices and the instruments for measuring them, both basic elements for pursuing research questions.
A 2021 American Thoracic Society workshop report (AE Holland, https://doi.org/10.1513/AnnalsATS.202102-146ST) identified essential components of a pulmonary rehabilitation model through an online Delphi process involving about 50 international experts. Components ultimately included those with median scores of 2 or higher (strongly agree or agree that the item is essential) and high consensus (interquartile range, 0). Thirteen essential components fit into four categories (Patient Assessment, Program Components, Method of Delivery and Quality Assurance). The Patient Assessment category included seven items: (1) An initial center-based assessment by a health care professional, (2) An exercise test at the time of assessment, (3) A field exercise test, (4) Quality of life measure, (5) Dyspnea assessment, (6) Nutritional status evaluation, and (7) Occupational status evaluation. The Program Components: (8) Endurance training and (9) Resistance training). The Method of Delivery: (10) An exercise program that is individually prescribed, (11) An exercise program that is individually progressed, and (12) Team includes a health care professional with experience in exercise prescription and progression. The single Quality Assurance item: (13) Health care professionals are trained to deliver the components of the model that is deployed.
Cochrane Library review
2021 “Intervention Review” (“Telerehabilitation for chronic respiratory disease,” https://doi.org/10.1002/14651858.CD013040.pub2). Using their own databases (eg, Cochrane Airways Trials Register) and others, the authors included controlled trials published up to November 30, 2020 with at least 50% of the rehabilitation delivered by telerehabilitation. The authors’ analysis of 15 studies (with 32 reports) including 1904 participants (99% with COPD): “There was probably little or no difference between telerehabilitation and in-person pulmonary rehabilitation for exercise capacity measured as 6-Minute Walking Distance (mean difference 0.06 meters (m), 95% confidence interval (CI) -10.82 m to 10.94 m).” They reached the same conclusion for quality of life, and for breathlessness. Completion of rehabilitation programs, however, was more likely with telerehabilitation at 93% versus 70% for in-person rehabilitation. No adverse effects of telerehabilitation were observed over and above those for in-person or no rehabilitation. An obvious limitation of the findings is that the studies all pre-date COVID-19, which would have introduced very significant disincentives for in-person rehabilitation completion.
An older (2016) international randomized controlled study (Zanaboni et al, https://doi.org/10.1186/s12890-016-0288-z) comparing long-term telerehabilitation or unsupervised treadmill training at home with standard care included 120 participants with COPD and had 2-years of follow-up. Telerehabilitation consisted of individualized treadmill training at home. Participants had scheduled exercise sessions supervised by a physiotherapist via videoconferencing following a standardized protocol. Participants in the unsupervised training group were provided with a treadmill only to perform unsupervised exercise at home. They also received an exercise booklet, a paper exercise diary to record their training sessions, and an individualized training program but without regular review or progression of the program. For the primary outcomes of combined hospitalizations and emergency department presentations, incidence rate of hospitalizations and emergency department presentations was lower with telerehabilitation (1.18 events per person-year; 95% confidence interval [CI], 0.94–1.46) and with unsupervised training group (1.14; 95% CI, 0.92–1.41) than in the control group (1.88; 95% CI, 1.58–2.21; P < .001 compared with intervention groups). Both training groups had better health status at 1-year, and achieved and maintained clinically significant improvements in exercise capacity.
Access to pulmonary rehabilitation
Continuing evidence of clear telerehabilitation benefits is good news, especially in the light of impediments to attendance at in-clinic programs. Although the COVID-provoked disincentives have been diminishing, persisting access issues remain for substantial portions of eligible populations, according to a recent (2024) cross-sectional study (PA Kahn, WA Mathis, doi:10.1001/jamanetworkopen.2023.54867) looking at travel time to pulmonary rehabilitation programs as a marker for pulmonary rehabilitation access. The report, based on US Census designations (lower 48 states and Washington, D.C.) found that while 80.3% of the population lives in urban or suburban areas within a 30-minute drive of a pulmonary rehabilitation program, travel time exceeds that in rural and other sparsely populated areas with more than 14 million people residing in areas demanding more than 1-hour for travel. A further analysis showed also that nearly 30% of American Indian and Alaska Native populations live more than 60 minutes from a pulmonary rehabilitation program.
Aside from the obvious restraints for homebound patients or those lacking transportation or who need medical transport, other common impediments inhibit on-site pulmonary rehabilitation attendance, said Corinne Young, MSN, FNP-C, FCCP. Ms. Young is the director of Advance Practice Provider and Clinical Services for Colorado Springs Pulmonary Consultants, president and founder of the Association of Pulmonary Advance Practice Providers, and a member of the CHEST Physician Editorial Board. “I have some patients who say ‘There’s no way I could do onsite pulmonary rehab because of my knee — or back, or shoulder.’ But in their own home environment they may feel more comfortable. They may be willing to try new things at their own pace, whereas for them a program may feel too regimented.” For others, Ms. Young said, aspects of a formal program are a clear plus factor. “They love to hear their progress at the end of — say a 12-week program — where their virtual respiratory therapist records and reports to them their six-minute walk and other test results. Feedback is a great reinforcer.” Quality of life improvements, Ms. Young commented, were one of the very impressive benefits that appeared in the initial studies of pulmonary rehabilitation for COPD patients. “Being patient-centric, you want to improve quality of life for them as much as possible and we see telerehabilitation as a great opportunity for many,” she added.
“I would like to see head-to-head data on outpatient versus at-home pulmonary rehabilitation on hospitalizations, time to exacerbation and, of course, mortality. We have all that for outpatient rehab, but it would be great to be able to compare them. Knowing that would influence what we recommend, especially for patients who could go either way. Also, you have to assess their motivation and discipline to know who might be more appropriate for unsupervised pulmonary rehabilitation.”
The current reality for Ms. Young is that in her Colorado Springs vicinity, where both in-patient programs are only 15 minutes apart, she knows of no telerehabilitation programs being offered. While there are contract telerehabilitation providers, Young said, and her organization (The Association of Pulmonary Advanced Practice Providers) has been approached by one, none are licensed in Colorado, and telerehabilitation is not a billable service.
“As of yet, I’m not aware of any telemedicine pulmonary rehab available at our institution,” said pulmonologist Mary Jo S. Farmer, MD, PhD, FCCP, Associate Professor of Medicine at UMass Chan Medical School – Baystate, Springfield, MA, and a member of the CHEST Physician Editorial Board. A brief internet search identified a telerehabilitation contract provider available only in Arizona.
Reimbursement will also be a foundational concern, Ms. Young commented. While a physician, nurse practitioner, or physician virtual visit for education may be billable, telerehabilitation reimbursement is new territory. “How that all is going to work out is a big unknown piece,” she said.
Minimal components
Effective pulmonary telerehabilitation programs, Ms. Young said, need to provide exercise with an aerobic device, either a treadmill, a stationary bike or even a Cubii-type under desk foot pedal/elliptical machine, and some resistance training (elastic bands, or weights, for example). “But 50% of pulmonary rehabilitation is education about breathing techniques, purse-lip breathing, and pulmonary nutrition.” Also essential: one-on-one discussion with a qualified medical practitioner who checks on oximeter use, inhaler technique, and titrating oxygen therapy. “At our elevation of 6500 feet, most of our patients are on that.” Optimal frequency of encounters between providers and remote patients has to be elucidated by future research, Ms. Young said.
Ms. Young commented further, “With outpatient pulmonary rehabilitation there often isn’t a lot of one-on-one, but rather a big group of people exercising at the same time. I think actually there may be the potential to have more individualization with pulmonary telerehabilitation. But the barriers, the reimbursement/financial part, and the red tape and bureaucracy have to be worked on.”
As COVID-19 cedes its pandemic-scale status to the past, its wake is revealing surprises and raising questions, particularly in relation to pulmonary medicine. The need for isolation at COVID’s outset kept many millions at home, creating conditions favorable for the rapid expansion of technologies that were taken up quickly in telehealth applications. The need was overwhelming. But just how effective telehealth actually is at replacing on-site programs for COPD pulmonary rehab has remained a research challenge, although results from early studies show unmistakable value. Creating conditions conducive to research into the strengths and weaknesses of pulmonary rehab, and determining how research can be applied effectively, remain formidable challenges.
Early studies of telehealth pulmonary rehabilitation have not uncovered any glaring erosion of pulmonary rehabilitation’s well-established benefits. But, at the same time, the relatively young field of pulmonary telerehabilitation for chronic obstructive pulmonary disease (COPD) has lacked coordinated efforts to determine its key practices and the instruments for measuring them, both basic elements for pursuing research questions.
A 2021 American Thoracic Society workshop report (AE Holland, https://doi.org/10.1513/AnnalsATS.202102-146ST) identified essential components of a pulmonary rehabilitation model through an online Delphi process involving about 50 international experts. Components ultimately included those with median scores of 2 or higher (strongly agree or agree that the item is essential) and high consensus (interquartile range, 0). Thirteen essential components fit into four categories (Patient Assessment, Program Components, Method of Delivery and Quality Assurance). The Patient Assessment category included seven items: (1) An initial center-based assessment by a health care professional, (2) An exercise test at the time of assessment, (3) A field exercise test, (4) Quality of life measure, (5) Dyspnea assessment, (6) Nutritional status evaluation, and (7) Occupational status evaluation. The Program Components: (8) Endurance training and (9) Resistance training). The Method of Delivery: (10) An exercise program that is individually prescribed, (11) An exercise program that is individually progressed, and (12) Team includes a health care professional with experience in exercise prescription and progression. The single Quality Assurance item: (13) Health care professionals are trained to deliver the components of the model that is deployed.
Cochrane Library review
2021 “Intervention Review” (“Telerehabilitation for chronic respiratory disease,” https://doi.org/10.1002/14651858.CD013040.pub2). Using their own databases (eg, Cochrane Airways Trials Register) and others, the authors included controlled trials published up to November 30, 2020 with at least 50% of the rehabilitation delivered by telerehabilitation. The authors’ analysis of 15 studies (with 32 reports) including 1904 participants (99% with COPD): “There was probably little or no difference between telerehabilitation and in-person pulmonary rehabilitation for exercise capacity measured as 6-Minute Walking Distance (mean difference 0.06 meters (m), 95% confidence interval (CI) -10.82 m to 10.94 m).” They reached the same conclusion for quality of life, and for breathlessness. Completion of rehabilitation programs, however, was more likely with telerehabilitation at 93% versus 70% for in-person rehabilitation. No adverse effects of telerehabilitation were observed over and above those for in-person or no rehabilitation. An obvious limitation of the findings is that the studies all pre-date COVID-19, which would have introduced very significant disincentives for in-person rehabilitation completion.
An older (2016) international randomized controlled study (Zanaboni et al, https://doi.org/10.1186/s12890-016-0288-z) comparing long-term telerehabilitation or unsupervised treadmill training at home with standard care included 120 participants with COPD and had 2-years of follow-up. Telerehabilitation consisted of individualized treadmill training at home. Participants had scheduled exercise sessions supervised by a physiotherapist via videoconferencing following a standardized protocol. Participants in the unsupervised training group were provided with a treadmill only to perform unsupervised exercise at home. They also received an exercise booklet, a paper exercise diary to record their training sessions, and an individualized training program but without regular review or progression of the program. For the primary outcomes of combined hospitalizations and emergency department presentations, incidence rate of hospitalizations and emergency department presentations was lower with telerehabilitation (1.18 events per person-year; 95% confidence interval [CI], 0.94–1.46) and with unsupervised training group (1.14; 95% CI, 0.92–1.41) than in the control group (1.88; 95% CI, 1.58–2.21; P < .001 compared with intervention groups). Both training groups had better health status at 1-year, and achieved and maintained clinically significant improvements in exercise capacity.
Access to pulmonary rehabilitation
Continuing evidence of clear telerehabilitation benefits is good news, especially in the light of impediments to attendance at in-clinic programs. Although the COVID-provoked disincentives have been diminishing, persisting access issues remain for substantial portions of eligible populations, according to a recent (2024) cross-sectional study (PA Kahn, WA Mathis, doi:10.1001/jamanetworkopen.2023.54867) looking at travel time to pulmonary rehabilitation programs as a marker for pulmonary rehabilitation access. The report, based on US Census designations (lower 48 states and Washington, D.C.) found that while 80.3% of the population lives in urban or suburban areas within a 30-minute drive of a pulmonary rehabilitation program, travel time exceeds that in rural and other sparsely populated areas with more than 14 million people residing in areas demanding more than 1-hour for travel. A further analysis showed also that nearly 30% of American Indian and Alaska Native populations live more than 60 minutes from a pulmonary rehabilitation program.
Aside from the obvious restraints for homebound patients or those lacking transportation or who need medical transport, other common impediments inhibit on-site pulmonary rehabilitation attendance, said Corinne Young, MSN, FNP-C, FCCP. Ms. Young is the director of Advance Practice Provider and Clinical Services for Colorado Springs Pulmonary Consultants, president and founder of the Association of Pulmonary Advance Practice Providers, and a member of the CHEST Physician Editorial Board. “I have some patients who say ‘There’s no way I could do onsite pulmonary rehab because of my knee — or back, or shoulder.’ But in their own home environment they may feel more comfortable. They may be willing to try new things at their own pace, whereas for them a program may feel too regimented.” For others, Ms. Young said, aspects of a formal program are a clear plus factor. “They love to hear their progress at the end of — say a 12-week program — where their virtual respiratory therapist records and reports to them their six-minute walk and other test results. Feedback is a great reinforcer.” Quality of life improvements, Ms. Young commented, were one of the very impressive benefits that appeared in the initial studies of pulmonary rehabilitation for COPD patients. “Being patient-centric, you want to improve quality of life for them as much as possible and we see telerehabilitation as a great opportunity for many,” she added.
“I would like to see head-to-head data on outpatient versus at-home pulmonary rehabilitation on hospitalizations, time to exacerbation and, of course, mortality. We have all that for outpatient rehab, but it would be great to be able to compare them. Knowing that would influence what we recommend, especially for patients who could go either way. Also, you have to assess their motivation and discipline to know who might be more appropriate for unsupervised pulmonary rehabilitation.”
The current reality for Ms. Young is that in her Colorado Springs vicinity, where both in-patient programs are only 15 minutes apart, she knows of no telerehabilitation programs being offered. While there are contract telerehabilitation providers, Young said, and her organization (The Association of Pulmonary Advanced Practice Providers) has been approached by one, none are licensed in Colorado, and telerehabilitation is not a billable service.
“As of yet, I’m not aware of any telemedicine pulmonary rehab available at our institution,” said pulmonologist Mary Jo S. Farmer, MD, PhD, FCCP, Associate Professor of Medicine at UMass Chan Medical School – Baystate, Springfield, MA, and a member of the CHEST Physician Editorial Board. A brief internet search identified a telerehabilitation contract provider available only in Arizona.
Reimbursement will also be a foundational concern, Ms. Young commented. While a physician, nurse practitioner, or physician virtual visit for education may be billable, telerehabilitation reimbursement is new territory. “How that all is going to work out is a big unknown piece,” she said.
Minimal components
Effective pulmonary telerehabilitation programs, Ms. Young said, need to provide exercise with an aerobic device, either a treadmill, a stationary bike or even a Cubii-type under desk foot pedal/elliptical machine, and some resistance training (elastic bands, or weights, for example). “But 50% of pulmonary rehabilitation is education about breathing techniques, purse-lip breathing, and pulmonary nutrition.” Also essential: one-on-one discussion with a qualified medical practitioner who checks on oximeter use, inhaler technique, and titrating oxygen therapy. “At our elevation of 6500 feet, most of our patients are on that.” Optimal frequency of encounters between providers and remote patients has to be elucidated by future research, Ms. Young said.
Ms. Young commented further, “With outpatient pulmonary rehabilitation there often isn’t a lot of one-on-one, but rather a big group of people exercising at the same time. I think actually there may be the potential to have more individualization with pulmonary telerehabilitation. But the barriers, the reimbursement/financial part, and the red tape and bureaucracy have to be worked on.”
As COVID-19 cedes its pandemic-scale status to the past, its wake is revealing surprises and raising questions, particularly in relation to pulmonary medicine. The need for isolation at COVID’s outset kept many millions at home, creating conditions favorable for the rapid expansion of technologies that were taken up quickly in telehealth applications. The need was overwhelming. But just how effective telehealth actually is at replacing on-site programs for COPD pulmonary rehab has remained a research challenge, although results from early studies show unmistakable value. Creating conditions conducive to research into the strengths and weaknesses of pulmonary rehab, and determining how research can be applied effectively, remain formidable challenges.
Early studies of telehealth pulmonary rehabilitation have not uncovered any glaring erosion of pulmonary rehabilitation’s well-established benefits. But, at the same time, the relatively young field of pulmonary telerehabilitation for chronic obstructive pulmonary disease (COPD) has lacked coordinated efforts to determine its key practices and the instruments for measuring them, both basic elements for pursuing research questions.
A 2021 American Thoracic Society workshop report (AE Holland, https://doi.org/10.1513/AnnalsATS.202102-146ST) identified essential components of a pulmonary rehabilitation model through an online Delphi process involving about 50 international experts. Components ultimately included those with median scores of 2 or higher (strongly agree or agree that the item is essential) and high consensus (interquartile range, 0). Thirteen essential components fit into four categories (Patient Assessment, Program Components, Method of Delivery and Quality Assurance). The Patient Assessment category included seven items: (1) An initial center-based assessment by a health care professional, (2) An exercise test at the time of assessment, (3) A field exercise test, (4) Quality of life measure, (5) Dyspnea assessment, (6) Nutritional status evaluation, and (7) Occupational status evaluation. The Program Components: (8) Endurance training and (9) Resistance training). The Method of Delivery: (10) An exercise program that is individually prescribed, (11) An exercise program that is individually progressed, and (12) Team includes a health care professional with experience in exercise prescription and progression. The single Quality Assurance item: (13) Health care professionals are trained to deliver the components of the model that is deployed.
Cochrane Library review
2021 “Intervention Review” (“Telerehabilitation for chronic respiratory disease,” https://doi.org/10.1002/14651858.CD013040.pub2). Using their own databases (eg, Cochrane Airways Trials Register) and others, the authors included controlled trials published up to November 30, 2020 with at least 50% of the rehabilitation delivered by telerehabilitation. The authors’ analysis of 15 studies (with 32 reports) including 1904 participants (99% with COPD): “There was probably little or no difference between telerehabilitation and in-person pulmonary rehabilitation for exercise capacity measured as 6-Minute Walking Distance (mean difference 0.06 meters (m), 95% confidence interval (CI) -10.82 m to 10.94 m).” They reached the same conclusion for quality of life, and for breathlessness. Completion of rehabilitation programs, however, was more likely with telerehabilitation at 93% versus 70% for in-person rehabilitation. No adverse effects of telerehabilitation were observed over and above those for in-person or no rehabilitation. An obvious limitation of the findings is that the studies all pre-date COVID-19, which would have introduced very significant disincentives for in-person rehabilitation completion.
An older (2016) international randomized controlled study (Zanaboni et al, https://doi.org/10.1186/s12890-016-0288-z) comparing long-term telerehabilitation or unsupervised treadmill training at home with standard care included 120 participants with COPD and had 2-years of follow-up. Telerehabilitation consisted of individualized treadmill training at home. Participants had scheduled exercise sessions supervised by a physiotherapist via videoconferencing following a standardized protocol. Participants in the unsupervised training group were provided with a treadmill only to perform unsupervised exercise at home. They also received an exercise booklet, a paper exercise diary to record their training sessions, and an individualized training program but without regular review or progression of the program. For the primary outcomes of combined hospitalizations and emergency department presentations, incidence rate of hospitalizations and emergency department presentations was lower with telerehabilitation (1.18 events per person-year; 95% confidence interval [CI], 0.94–1.46) and with unsupervised training group (1.14; 95% CI, 0.92–1.41) than in the control group (1.88; 95% CI, 1.58–2.21; P < .001 compared with intervention groups). Both training groups had better health status at 1-year, and achieved and maintained clinically significant improvements in exercise capacity.
Access to pulmonary rehabilitation
Continuing evidence of clear telerehabilitation benefits is good news, especially in the light of impediments to attendance at in-clinic programs. Although the COVID-provoked disincentives have been diminishing, persisting access issues remain for substantial portions of eligible populations, according to a recent (2024) cross-sectional study (PA Kahn, WA Mathis, doi:10.1001/jamanetworkopen.2023.54867) looking at travel time to pulmonary rehabilitation programs as a marker for pulmonary rehabilitation access. The report, based on US Census designations (lower 48 states and Washington, D.C.) found that while 80.3% of the population lives in urban or suburban areas within a 30-minute drive of a pulmonary rehabilitation program, travel time exceeds that in rural and other sparsely populated areas with more than 14 million people residing in areas demanding more than 1-hour for travel. A further analysis showed also that nearly 30% of American Indian and Alaska Native populations live more than 60 minutes from a pulmonary rehabilitation program.
Aside from the obvious restraints for homebound patients or those lacking transportation or who need medical transport, other common impediments inhibit on-site pulmonary rehabilitation attendance, said Corinne Young, MSN, FNP-C, FCCP. Ms. Young is the director of Advance Practice Provider and Clinical Services for Colorado Springs Pulmonary Consultants, president and founder of the Association of Pulmonary Advance Practice Providers, and a member of the CHEST Physician Editorial Board. “I have some patients who say ‘There’s no way I could do onsite pulmonary rehab because of my knee — or back, or shoulder.’ But in their own home environment they may feel more comfortable. They may be willing to try new things at their own pace, whereas for them a program may feel too regimented.” For others, Ms. Young said, aspects of a formal program are a clear plus factor. “They love to hear their progress at the end of — say a 12-week program — where their virtual respiratory therapist records and reports to them their six-minute walk and other test results. Feedback is a great reinforcer.” Quality of life improvements, Ms. Young commented, were one of the very impressive benefits that appeared in the initial studies of pulmonary rehabilitation for COPD patients. “Being patient-centric, you want to improve quality of life for them as much as possible and we see telerehabilitation as a great opportunity for many,” she added.
“I would like to see head-to-head data on outpatient versus at-home pulmonary rehabilitation on hospitalizations, time to exacerbation and, of course, mortality. We have all that for outpatient rehab, but it would be great to be able to compare them. Knowing that would influence what we recommend, especially for patients who could go either way. Also, you have to assess their motivation and discipline to know who might be more appropriate for unsupervised pulmonary rehabilitation.”
The current reality for Ms. Young is that in her Colorado Springs vicinity, where both in-patient programs are only 15 minutes apart, she knows of no telerehabilitation programs being offered. While there are contract telerehabilitation providers, Young said, and her organization (The Association of Pulmonary Advanced Practice Providers) has been approached by one, none are licensed in Colorado, and telerehabilitation is not a billable service.
“As of yet, I’m not aware of any telemedicine pulmonary rehab available at our institution,” said pulmonologist Mary Jo S. Farmer, MD, PhD, FCCP, Associate Professor of Medicine at UMass Chan Medical School – Baystate, Springfield, MA, and a member of the CHEST Physician Editorial Board. A brief internet search identified a telerehabilitation contract provider available only in Arizona.
Reimbursement will also be a foundational concern, Ms. Young commented. While a physician, nurse practitioner, or physician virtual visit for education may be billable, telerehabilitation reimbursement is new territory. “How that all is going to work out is a big unknown piece,” she said.
Minimal components
Effective pulmonary telerehabilitation programs, Ms. Young said, need to provide exercise with an aerobic device, either a treadmill, a stationary bike or even a Cubii-type under desk foot pedal/elliptical machine, and some resistance training (elastic bands, or weights, for example). “But 50% of pulmonary rehabilitation is education about breathing techniques, purse-lip breathing, and pulmonary nutrition.” Also essential: one-on-one discussion with a qualified medical practitioner who checks on oximeter use, inhaler technique, and titrating oxygen therapy. “At our elevation of 6500 feet, most of our patients are on that.” Optimal frequency of encounters between providers and remote patients has to be elucidated by future research, Ms. Young said.
Ms. Young commented further, “With outpatient pulmonary rehabilitation there often isn’t a lot of one-on-one, but rather a big group of people exercising at the same time. I think actually there may be the potential to have more individualization with pulmonary telerehabilitation. But the barriers, the reimbursement/financial part, and the red tape and bureaucracy have to be worked on.”
Military burn pits: Their evidence and implications for respiratory health
Military service is a hazard-ridden profession. It’s easy to recognize the direct dangers from warfighting, such as gunfire and explosions, but the risks from environmental, chemical, and other occupational exposures can be harder to see.
Combustion-based waste management systems, otherwise known as “burn pits,” were used in deployed environments by the US military from the 1990s to the early 2010s. These burn pits were commonly used to eliminate plastics, electronics, munitions, metals, wood, chemicals, and even human waste. At the height of the recent conflicts in Afghanistan, Iraq, and other southwest Asia locations, more than 70% of military installations employed at least one, and nearly 4 million service members were exposed to some degree to their emissions.
Reports of burn pits being related to organic disease have garnered widespread media attention. Initially, this came through anecdotal reports of post-deployment respiratory symptoms. Over time, the conditions attributed to burn pits expanded to include newly diagnosed respiratory diseases and malignancies.
Ultimately, Congress passed the 2022 Promise to Address Comprehensive Toxins (PACT) Act, presumptively linking more than 20 diagnoses to burn pits. The PACT Act provides countless veterans access to low-cost or free medical care for their respective conditions.
What do we know about burn pits and deployment-related respiratory disease?
Data from the Millennium Cohort Study noted an approximately 40% increase in respiratory symptoms among individuals returning from deployment but no increase in the frequency of diagnosed respiratory diseases.1 This study and others definitively established a temporal relationship between deployment and respiratory symptoms. Soon after, a retrospective, observational study of service members with post-deployment respiratory symptoms found a high prevalence of constrictive bronchiolitis (CB) identified by lung biopsy.2 Patients in this group reported exposure to burn pits and a sulfur mine fire in the Mosul area while deployed. Most had normal imaging and pulmonary function testing before biopsy, confounding the clinical significance of the CB finding. The publication of this report led to increased investigation of respiratory function during and after deployment.
In a series of prospective studies that included full pulmonary function testing, impulse oscillometry, cardiopulmonary exercise testing, bronchoscopy, and, occasionally, lung biopsy to evaluate post-deployment dyspnea, only a small minority received a diagnosis of clinically significant lung disease.3,4 Additionally, when comparing spirometry and impulse oscillometry results from before and after deployment, no decline in lung function was observed in a population of service members reporting regular burn pit exposure.5 These studies suggest that at the population level, deployment does not lead to abnormalities in the structure and function of the respiratory system.
The National Academies of Sciences published two separate reviews of burn pit exposure and outcomes in 2011 and 2020.6,7 They found insufficient evidence to support a causal relationship between burn pit exposure and pulmonary disease. They highlighted studies on the composition of emissions from the area surrounding the largest military burn pit in Iraq. Levels of particulate matter, volatile organic compounds, and polycyclic aromatic hydrocarbons were elevated when compared with those of a typical American city but were similar to the pollution levels seen in the region at the time. Given these findings, they suggested ambient air pollution may have contributed more to clinically significant disease than burn pit emissions.
How do we interpret this mixed data?
At the population level, we have yet to find conclusive data directly linking burn pit exposure to the development of any respiratory disease. Does this mean that burn pits are not harmful?
Not necessarily. Research on outcomes related to burn pit exposure is challenging given the heterogeneity in exposure volume. Much of the research is retrospective and subject to recall bias. Relationships may be distorted, and the precision of reported symptoms and exposure levels is altered. Given these challenges, it’s unsurprising that evidence of causality has yet to be proven. In addition, some portion of service members has been diagnosed with respiratory disease that could be related to burn pit exposure.
What is now indisputable is that deployment to southwest Asia leads to an increase in respiratory complaints. Whether veteran respiratory symptoms are due to burn pits, ambient pollution, environmental particulate matter, or dust storms is less clinically relevant. These symptoms require attention, investigation, and management.
What does this mean for the future medical care of service members and veterans?
Many veterans with post-deployment respiratory symptoms undergo extensive evaluations without obtaining a definitive diagnosis. A recent consensus statement on deployment-related respiratory symptoms provides a framework for evaluation in such cases.8 In keeping with that statement, we recommend veterans be referred to centers with expertise in this field, such as the Department of Veterans Affairs (VA) or military health centers, when deployment-related respiratory symptoms are reported. When the evaluation does not lead to a treatable diagnosis, these centers can provide multidisciplinary care to address the symptoms of dyspnea, cough, fatigue, and exercise intolerance to improve functional status.
Despite uncertainty in the evidence or challenges in diagnosis, both the Department of Defense (DoD) and VA remain fully committed to addressing the health concerns of service members and veterans. Notably, the VA has already screened more than 5 million veterans for toxic military exposures in accordance with the PACT Act and is providing ongoing screening and care for veterans with post-deployment respiratory symptoms. Furthermore, the DoD and VA have dedicated large portions of their research budgets to investigating the impacts of exposures during military service and optimizing the care of those with respiratory symptoms. With these commitments to patient care and research, our veterans’ respiratory health can now be optimized, and future risks can be mitigated.
Dr. Haynes is Fellow, Pulmonary and Critical Care Medicine, Walter Reed National Military Medical Center, Assistant Professor of Medicine, Uniformed Services University. Dr. Nations is Pulmonary and Critical Care Medicine, Deputy Chief of Staff for Operations, Washington DC VA Medical Center, Associate Professor of Medicine, Uniformed Services University.
References
1. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. Preprint. Posted online October 22, 2009. PMID: 19850627. doi: 10.1093/aje/kwp287
2. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. Erratum in: N Engl J Med. 2011;365(18):1749. PMID: 21774710; PMCID: PMC3296566. doi: 10.1056/NEJMoa1101388
3. Morris MJ, Dodson DW, Lucero PF, et al. Study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE). Am J Respir Crit Care Med. 2014;190(1):77-84. PMID: 24922562. doi: 10.1164/rccm.201402-0372OC
4. Morris MJ, Walter RJ, McCann ET, et al. Clinical evaluation of deployed military personnel with chronic respiratory symptoms: study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE) III. Chest. 2020;157(6):1559-1567. Preprint. Posted online February 1, 2020. PMID: 32017933. doi: 10.1016/j.chest.2020.01.024
5. Morris MJ, Skabelund AJ, Rawlins FA 3rd, Gallup RA, Aden JK, Holley AB. Study of active duty military personnel for environmental deployment exposures: pre- and post-deployment spirometry (STAMPEDE II). Respir Care. 2019;64(5):536-544. Preprint. Posted online January 8, 2019.PMID: 30622173. doi: 10.4187/respcare.06396
6. Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. https://doi.org/10.17226/13209
7. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. https://doi.org/10.17226/25837
8. Falvo MJ, Sotolongo AM, Osterholzer JJ, et al. Consensus statements on deployment-related respiratory disease, inclusive of constrictive bronchiolitis: a modified Delphi study. Chest. 2023;163(3):599-609. Preprint. Posted November 4, 2022. PMID: 36343686; PMCID: PMC10154857. doi: 10.1016/j.chest.2022.10.031
Military service is a hazard-ridden profession. It’s easy to recognize the direct dangers from warfighting, such as gunfire and explosions, but the risks from environmental, chemical, and other occupational exposures can be harder to see.
Combustion-based waste management systems, otherwise known as “burn pits,” were used in deployed environments by the US military from the 1990s to the early 2010s. These burn pits were commonly used to eliminate plastics, electronics, munitions, metals, wood, chemicals, and even human waste. At the height of the recent conflicts in Afghanistan, Iraq, and other southwest Asia locations, more than 70% of military installations employed at least one, and nearly 4 million service members were exposed to some degree to their emissions.
Reports of burn pits being related to organic disease have garnered widespread media attention. Initially, this came through anecdotal reports of post-deployment respiratory symptoms. Over time, the conditions attributed to burn pits expanded to include newly diagnosed respiratory diseases and malignancies.
Ultimately, Congress passed the 2022 Promise to Address Comprehensive Toxins (PACT) Act, presumptively linking more than 20 diagnoses to burn pits. The PACT Act provides countless veterans access to low-cost or free medical care for their respective conditions.
What do we know about burn pits and deployment-related respiratory disease?
Data from the Millennium Cohort Study noted an approximately 40% increase in respiratory symptoms among individuals returning from deployment but no increase in the frequency of diagnosed respiratory diseases.1 This study and others definitively established a temporal relationship between deployment and respiratory symptoms. Soon after, a retrospective, observational study of service members with post-deployment respiratory symptoms found a high prevalence of constrictive bronchiolitis (CB) identified by lung biopsy.2 Patients in this group reported exposure to burn pits and a sulfur mine fire in the Mosul area while deployed. Most had normal imaging and pulmonary function testing before biopsy, confounding the clinical significance of the CB finding. The publication of this report led to increased investigation of respiratory function during and after deployment.
In a series of prospective studies that included full pulmonary function testing, impulse oscillometry, cardiopulmonary exercise testing, bronchoscopy, and, occasionally, lung biopsy to evaluate post-deployment dyspnea, only a small minority received a diagnosis of clinically significant lung disease.3,4 Additionally, when comparing spirometry and impulse oscillometry results from before and after deployment, no decline in lung function was observed in a population of service members reporting regular burn pit exposure.5 These studies suggest that at the population level, deployment does not lead to abnormalities in the structure and function of the respiratory system.
The National Academies of Sciences published two separate reviews of burn pit exposure and outcomes in 2011 and 2020.6,7 They found insufficient evidence to support a causal relationship between burn pit exposure and pulmonary disease. They highlighted studies on the composition of emissions from the area surrounding the largest military burn pit in Iraq. Levels of particulate matter, volatile organic compounds, and polycyclic aromatic hydrocarbons were elevated when compared with those of a typical American city but were similar to the pollution levels seen in the region at the time. Given these findings, they suggested ambient air pollution may have contributed more to clinically significant disease than burn pit emissions.
How do we interpret this mixed data?
At the population level, we have yet to find conclusive data directly linking burn pit exposure to the development of any respiratory disease. Does this mean that burn pits are not harmful?
Not necessarily. Research on outcomes related to burn pit exposure is challenging given the heterogeneity in exposure volume. Much of the research is retrospective and subject to recall bias. Relationships may be distorted, and the precision of reported symptoms and exposure levels is altered. Given these challenges, it’s unsurprising that evidence of causality has yet to be proven. In addition, some portion of service members has been diagnosed with respiratory disease that could be related to burn pit exposure.
What is now indisputable is that deployment to southwest Asia leads to an increase in respiratory complaints. Whether veteran respiratory symptoms are due to burn pits, ambient pollution, environmental particulate matter, or dust storms is less clinically relevant. These symptoms require attention, investigation, and management.
What does this mean for the future medical care of service members and veterans?
Many veterans with post-deployment respiratory symptoms undergo extensive evaluations without obtaining a definitive diagnosis. A recent consensus statement on deployment-related respiratory symptoms provides a framework for evaluation in such cases.8 In keeping with that statement, we recommend veterans be referred to centers with expertise in this field, such as the Department of Veterans Affairs (VA) or military health centers, when deployment-related respiratory symptoms are reported. When the evaluation does not lead to a treatable diagnosis, these centers can provide multidisciplinary care to address the symptoms of dyspnea, cough, fatigue, and exercise intolerance to improve functional status.
Despite uncertainty in the evidence or challenges in diagnosis, both the Department of Defense (DoD) and VA remain fully committed to addressing the health concerns of service members and veterans. Notably, the VA has already screened more than 5 million veterans for toxic military exposures in accordance with the PACT Act and is providing ongoing screening and care for veterans with post-deployment respiratory symptoms. Furthermore, the DoD and VA have dedicated large portions of their research budgets to investigating the impacts of exposures during military service and optimizing the care of those with respiratory symptoms. With these commitments to patient care and research, our veterans’ respiratory health can now be optimized, and future risks can be mitigated.
Dr. Haynes is Fellow, Pulmonary and Critical Care Medicine, Walter Reed National Military Medical Center, Assistant Professor of Medicine, Uniformed Services University. Dr. Nations is Pulmonary and Critical Care Medicine, Deputy Chief of Staff for Operations, Washington DC VA Medical Center, Associate Professor of Medicine, Uniformed Services University.
References
1. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. Preprint. Posted online October 22, 2009. PMID: 19850627. doi: 10.1093/aje/kwp287
2. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. Erratum in: N Engl J Med. 2011;365(18):1749. PMID: 21774710; PMCID: PMC3296566. doi: 10.1056/NEJMoa1101388
3. Morris MJ, Dodson DW, Lucero PF, et al. Study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE). Am J Respir Crit Care Med. 2014;190(1):77-84. PMID: 24922562. doi: 10.1164/rccm.201402-0372OC
4. Morris MJ, Walter RJ, McCann ET, et al. Clinical evaluation of deployed military personnel with chronic respiratory symptoms: study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE) III. Chest. 2020;157(6):1559-1567. Preprint. Posted online February 1, 2020. PMID: 32017933. doi: 10.1016/j.chest.2020.01.024
5. Morris MJ, Skabelund AJ, Rawlins FA 3rd, Gallup RA, Aden JK, Holley AB. Study of active duty military personnel for environmental deployment exposures: pre- and post-deployment spirometry (STAMPEDE II). Respir Care. 2019;64(5):536-544. Preprint. Posted online January 8, 2019.PMID: 30622173. doi: 10.4187/respcare.06396
6. Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. https://doi.org/10.17226/13209
7. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. https://doi.org/10.17226/25837
8. Falvo MJ, Sotolongo AM, Osterholzer JJ, et al. Consensus statements on deployment-related respiratory disease, inclusive of constrictive bronchiolitis: a modified Delphi study. Chest. 2023;163(3):599-609. Preprint. Posted November 4, 2022. PMID: 36343686; PMCID: PMC10154857. doi: 10.1016/j.chest.2022.10.031
Military service is a hazard-ridden profession. It’s easy to recognize the direct dangers from warfighting, such as gunfire and explosions, but the risks from environmental, chemical, and other occupational exposures can be harder to see.
Combustion-based waste management systems, otherwise known as “burn pits,” were used in deployed environments by the US military from the 1990s to the early 2010s. These burn pits were commonly used to eliminate plastics, electronics, munitions, metals, wood, chemicals, and even human waste. At the height of the recent conflicts in Afghanistan, Iraq, and other southwest Asia locations, more than 70% of military installations employed at least one, and nearly 4 million service members were exposed to some degree to their emissions.
Reports of burn pits being related to organic disease have garnered widespread media attention. Initially, this came through anecdotal reports of post-deployment respiratory symptoms. Over time, the conditions attributed to burn pits expanded to include newly diagnosed respiratory diseases and malignancies.
Ultimately, Congress passed the 2022 Promise to Address Comprehensive Toxins (PACT) Act, presumptively linking more than 20 diagnoses to burn pits. The PACT Act provides countless veterans access to low-cost or free medical care for their respective conditions.
What do we know about burn pits and deployment-related respiratory disease?
Data from the Millennium Cohort Study noted an approximately 40% increase in respiratory symptoms among individuals returning from deployment but no increase in the frequency of diagnosed respiratory diseases.1 This study and others definitively established a temporal relationship between deployment and respiratory symptoms. Soon after, a retrospective, observational study of service members with post-deployment respiratory symptoms found a high prevalence of constrictive bronchiolitis (CB) identified by lung biopsy.2 Patients in this group reported exposure to burn pits and a sulfur mine fire in the Mosul area while deployed. Most had normal imaging and pulmonary function testing before biopsy, confounding the clinical significance of the CB finding. The publication of this report led to increased investigation of respiratory function during and after deployment.
In a series of prospective studies that included full pulmonary function testing, impulse oscillometry, cardiopulmonary exercise testing, bronchoscopy, and, occasionally, lung biopsy to evaluate post-deployment dyspnea, only a small minority received a diagnosis of clinically significant lung disease.3,4 Additionally, when comparing spirometry and impulse oscillometry results from before and after deployment, no decline in lung function was observed in a population of service members reporting regular burn pit exposure.5 These studies suggest that at the population level, deployment does not lead to abnormalities in the structure and function of the respiratory system.
The National Academies of Sciences published two separate reviews of burn pit exposure and outcomes in 2011 and 2020.6,7 They found insufficient evidence to support a causal relationship between burn pit exposure and pulmonary disease. They highlighted studies on the composition of emissions from the area surrounding the largest military burn pit in Iraq. Levels of particulate matter, volatile organic compounds, and polycyclic aromatic hydrocarbons were elevated when compared with those of a typical American city but were similar to the pollution levels seen in the region at the time. Given these findings, they suggested ambient air pollution may have contributed more to clinically significant disease than burn pit emissions.
How do we interpret this mixed data?
At the population level, we have yet to find conclusive data directly linking burn pit exposure to the development of any respiratory disease. Does this mean that burn pits are not harmful?
Not necessarily. Research on outcomes related to burn pit exposure is challenging given the heterogeneity in exposure volume. Much of the research is retrospective and subject to recall bias. Relationships may be distorted, and the precision of reported symptoms and exposure levels is altered. Given these challenges, it’s unsurprising that evidence of causality has yet to be proven. In addition, some portion of service members has been diagnosed with respiratory disease that could be related to burn pit exposure.
What is now indisputable is that deployment to southwest Asia leads to an increase in respiratory complaints. Whether veteran respiratory symptoms are due to burn pits, ambient pollution, environmental particulate matter, or dust storms is less clinically relevant. These symptoms require attention, investigation, and management.
What does this mean for the future medical care of service members and veterans?
Many veterans with post-deployment respiratory symptoms undergo extensive evaluations without obtaining a definitive diagnosis. A recent consensus statement on deployment-related respiratory symptoms provides a framework for evaluation in such cases.8 In keeping with that statement, we recommend veterans be referred to centers with expertise in this field, such as the Department of Veterans Affairs (VA) or military health centers, when deployment-related respiratory symptoms are reported. When the evaluation does not lead to a treatable diagnosis, these centers can provide multidisciplinary care to address the symptoms of dyspnea, cough, fatigue, and exercise intolerance to improve functional status.
Despite uncertainty in the evidence or challenges in diagnosis, both the Department of Defense (DoD) and VA remain fully committed to addressing the health concerns of service members and veterans. Notably, the VA has already screened more than 5 million veterans for toxic military exposures in accordance with the PACT Act and is providing ongoing screening and care for veterans with post-deployment respiratory symptoms. Furthermore, the DoD and VA have dedicated large portions of their research budgets to investigating the impacts of exposures during military service and optimizing the care of those with respiratory symptoms. With these commitments to patient care and research, our veterans’ respiratory health can now be optimized, and future risks can be mitigated.
Dr. Haynes is Fellow, Pulmonary and Critical Care Medicine, Walter Reed National Military Medical Center, Assistant Professor of Medicine, Uniformed Services University. Dr. Nations is Pulmonary and Critical Care Medicine, Deputy Chief of Staff for Operations, Washington DC VA Medical Center, Associate Professor of Medicine, Uniformed Services University.
References
1. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. Preprint. Posted online October 22, 2009. PMID: 19850627. doi: 10.1093/aje/kwp287
2. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. Erratum in: N Engl J Med. 2011;365(18):1749. PMID: 21774710; PMCID: PMC3296566. doi: 10.1056/NEJMoa1101388
3. Morris MJ, Dodson DW, Lucero PF, et al. Study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE). Am J Respir Crit Care Med. 2014;190(1):77-84. PMID: 24922562. doi: 10.1164/rccm.201402-0372OC
4. Morris MJ, Walter RJ, McCann ET, et al. Clinical evaluation of deployed military personnel with chronic respiratory symptoms: study of active duty military for pulmonary disease related to environmental deployment exposures (STAMPEDE) III. Chest. 2020;157(6):1559-1567. Preprint. Posted online February 1, 2020. PMID: 32017933. doi: 10.1016/j.chest.2020.01.024
5. Morris MJ, Skabelund AJ, Rawlins FA 3rd, Gallup RA, Aden JK, Holley AB. Study of active duty military personnel for environmental deployment exposures: pre- and post-deployment spirometry (STAMPEDE II). Respir Care. 2019;64(5):536-544. Preprint. Posted online January 8, 2019.PMID: 30622173. doi: 10.4187/respcare.06396
6. Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. https://doi.org/10.17226/13209
7. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. https://doi.org/10.17226/25837
8. Falvo MJ, Sotolongo AM, Osterholzer JJ, et al. Consensus statements on deployment-related respiratory disease, inclusive of constrictive bronchiolitis: a modified Delphi study. Chest. 2023;163(3):599-609. Preprint. Posted November 4, 2022. PMID: 36343686; PMCID: PMC10154857. doi: 10.1016/j.chest.2022.10.031
AI Tools Could Change Pulmonological Imaging and Prognosis
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Diet and exercise improve cardiac function, QoL in PAH
SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.
In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.
The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.
“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.
Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.
Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
PHINE details
In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.
The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).
The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
Results
At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.
However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.
As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
Worth trying
Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.
“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.
“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.
The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.
SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.
In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.
The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.
“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.
Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.
Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
PHINE details
In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.
The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).
The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
Results
At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.
However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.
As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
Worth trying
Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.
“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.
“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.
The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.
SAN DIEGO — A lifestyle intervention focused on diet and exercise can improve cardiac function and the quality of life for patients with pulmonary arterial hypertension (PAH), results of a randomized clinical trial show.
In addition, for those participants in the diet and exercise group who lost weight, right ventricular glucose uptake improved, reported Gustavo A. Heresi, MD, MS of the division of pulmonary medicine at the Cleveland Clinic.
The intervention did not, however, have an effect on insulin sensitivity, suggesting that insulin resistance is not a significant pathological mechanism in PAH, he said in an oral abstract session at the American Thoracic Society’s international conference.
“With these data, in the context of prior studies showing the benefits of exercise interventions, we believe that diet and exercise should be incorporated and thought of as part of the treatment armamentarium for pulmonary arterial hypertension,” he said.
Despite the availability of 14 FDA-approved medications for PAH, the disease is incurable. It is marked by progressive pulmonary vasoconstriction, pulmonary vascular remodeling, fibrosis and inflammation, in situ thrombosis, and right ventricular failure.
Because abnormalities in both glucose and insulin metabolism are prevalent and associated with decreased survival in patients with PAH, Dr. Heresi and colleagues designed a randomized trial to test the hypothesis that a diet and exercise intervention could improve insulin sensitivity and right ventricular function.
PHINE details
In the study, dubbed Pulmonary Arterial Hypertension Improvement with Nutrition and Exercise (PHINE), the investigators enrolled adults with group 1 PAH who were stable on PAH medications for at least 2 months. Patients with portopulmonary hypertension, New York Heart Association (NYHA) class IV heart failure, syncope, or on supplemental oxygen greater than 4 liters per minute were excluded.
The patients were screened with a graded exercise test, intravenous glucose tolerance test, and other measures at baseline, and after stratification by NYHA class and tricuspid annular plane systolic excursion (TAPSE) score were randomized to the intervention arm (16 patients) or standard of care control arm (14 patients).
The intervention consisted of supervised exercise training for 50-60 minutes on a treadmill at 80%-85% of the patient’s maximum heart rate 5 days per week, plus weekly counseling on a combination low glycemic index/Mediterranean dietary pattern. The diet portion included olive oil as the primary fat source, three 1-ounce servings of nuts and peanuts weekly, fish and legumes at a minimum of 3 servings weekly, and no sugar-sweetened beverage, commercial bakery products, pastries, white breads, white rice, or white potatoes.
Results
At the conclusion of the study at 12 weeks there were no statistically significant differences between the groups in either insulin sensitivity or right ventricular strain.
However, patients in the intervention arm had significant improvements compared with controls in mean RV function as measured by TAPSE, improved exercise capacity as measured by peak oxygen uptake and 6-minute walking distance, quality of life as measured by EmPHasis-10 health-related quality of life score, and NYHA functional class.
As noted, right ventricular glucose uptake was improved among those patients in the intervention group who lost weight over the study period.
Worth trying
Ravi Kalhan, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, who co-moderated the session but was not involved in the study, said in an interview that the study results show promise.
“We’re so centered on what’s the next big pharmacotherapy you can give to fix the disease, but sometimes maybe we should be pushing lifestyle interventions that are impactful, and they have biologic mechanisms — it’s not just that you got in better shape, but right ventricular function also improves. I’m pretty drawn to that sort of thing,” he said.
“That’s a pretty major effect over a 3-month intervention,” agreed co-moderator Nuala J. Meyer, MD, MS, ATSF, of the Hospital of the University of Pennsylvania.
The PHINE trial was supported by National Institute of Health grants. Dr. Heresi, Dr. Kalhan, and Dr. Meyer reported no conflicts of interest.
FROM ATS 2024
LDCT Lung Cancer Screening Finds Undiagnosed Pulmonary Comorbidities in High-Risk Population
Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.
Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.
The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
Baseline LDCT for Identification of Comorbidities
Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.
Approximately half of the participants in both groups were female.
Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).
Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.
“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.
However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.
Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.
A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
Lung Cancer Screening May Promote Earlier COPD Intervention
The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.
“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.
“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.
The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.
“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.
“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.
Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.
“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.
“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.
Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.
A version of this article first appeared on Medscape.com.
Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.
Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.
The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
Baseline LDCT for Identification of Comorbidities
Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.
Approximately half of the participants in both groups were female.
Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).
Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.
“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.
However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.
Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.
A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
Lung Cancer Screening May Promote Earlier COPD Intervention
The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.
“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.
“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.
The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.
“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.
“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.
Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.
“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.
“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.
Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.
A version of this article first appeared on Medscape.com.
Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.
Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.
The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
Baseline LDCT for Identification of Comorbidities
Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.
Approximately half of the participants in both groups were female.
Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).
Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.
“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.
However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.
Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.
A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
Lung Cancer Screening May Promote Earlier COPD Intervention
The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.
“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.
“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.
The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.
“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.
“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.
Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.
“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.
“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.
Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.
A version of this article first appeared on Medscape.com.
Space: The final frontier of public health, air pollution data
SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).
In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.
“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.
“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.
The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”
Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.
NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.
Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
Monitoring pollution with TEMPO
There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.
TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.
Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO2,) formaldehyde, and aerosols.
More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.
Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO2 levels from cities, traffic corridors, power plants, oil and gas fields, and fires.
Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO2 concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
Fire and heat
Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.
NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.
Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.
Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.
Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).
NASA health and climate data are available at https://www.earthdata.nasa.gov/.
Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.
SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).
In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.
“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.
“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.
The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”
Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.
NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.
Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
Monitoring pollution with TEMPO
There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.
TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.
Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO2,) formaldehyde, and aerosols.
More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.
Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO2 levels from cities, traffic corridors, power plants, oil and gas fields, and fires.
Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO2 concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
Fire and heat
Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.
NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.
Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.
Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.
Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).
NASA health and climate data are available at https://www.earthdata.nasa.gov/.
Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.
SAN DIEGO – No matter where on earth you live, there’s likely to be an eye in the sky hovering overhead, and that’s a good thing, at least when it comes to satellite monitoring of air quality, said scientists from the National Aeronautics and Space Administration (NASA).
In a special symposium held at the American Thoracic Society’s international conference, NASA health and air quality specialists described the use of space-based systems and earth science applications to improve understanding of respiratory health risks worldwide, and to help enrich pulmonary research with galaxies of data.
“Every day we download over 25 terabytes of data,” said John Haynes, MS, program manager for Health and Air Quality Applications in the Earth Action Program of the NASA Earth Science Division in Washington.
“Many of the observation data sets are critical for healthy air quality applications: observation of land surface temperature, sea surface temperature, precipitation, fires and thermal anomalies, aerosols, just to name a few, and the really awesome news is this offering from our constellation of satellites is free and open access, available to everyone across the globe,” he said.
The mission of NASA’s Earth Action Program is “to enable people and organizations to apply insights from Earth science to benefit the economy, health, quality of life, and environment.”
Program staff work with both industry and nonprofit environmental advocacy and health groups to help inform their decisions and actions with Earth science information.
NASA supports the use of Earth observations to help monitor and manage infectious diseases and environmental health, toxins and pathogens that affect health, air quality standards, and to assess the effects of climate change on air quality and public health.
Mr. Haynes noted that worldwide, six major cities have incorporated NASA data on fine particulate matter smaller than 2.5 microns (PM2.5) into their climate action plans. These cities include Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; Guadalajara, Mexico; Lima, Peru; and Johannesburg, South Africa.
Monitoring pollution with TEMPO
There are more than 30 Earth-monitoring systems currently in orbit or soon to be launched, including NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO), launched in April 2023, with first operations in August 2023. The instrument is in a geostationary orbit about 22,236 miles above the equator at longitudes that allow it to survey virtually all of North America — from coast to coast, and from southern Mexico, Cuba, Puerto Rico, and the Bahamas to Northern Canada.
TEMPO is part of a geostationary air quality satellite “constellation” or group that provides daylight observation over the entire Northern Hemisphere, explained Aaron Naeger, PhD, MS, mission applications lead for TEMPO at the NASA Marshall Space Flight Center in Huntsville, Alabama.
Until TEMPO, space-based instruments had relatively low spatial resolution and could only capture one image each day. In contrast, TEMPO can scan east-west each daylight hour across its entire coverage area (known as the Field of Regard), and even more frequently during early morning and late afternoon. This allows researchers to measure volumes of pollution, sources, and how these pollution levels vary over time. The system measures ozone levels, nitrogen dioxide (NO2,) formaldehyde, and aerosols.
More than 100 federal, state, local and tribal air quality agencies use the data captured by TEMPO to inform public health efforts.
Dr. Naeger gave examples of how the system can help identify public health hazards, including scans that showed high NO2 levels from cities, traffic corridors, power plants, oil and gas fields, and fires.
Similarly, the system detected unhealthy ozone and PM2.5 levels during prescribed burns in April 2024, as well as notable differences between weekdays and weekends in NO2 concentrations across California and the Front Range in Colorado. These showed higher levels along traffic corridors during weekdays related to increased traffic volumes and tailpipe emissions.
Fire and heat
Other NASA health and air quality initiatives include the FireAQ project, based at the University of Iowa in Iowa City, which provides free online weekly briefings on fire-related air quality concerns using data from TEMPO and other NASA satellite systems. The FireAQ project was described by Jun Wang, PhD, from the University of Iowa in Iowa City.
NASA also fosters collaborations to reduce health disparities in air quality and respiratory health in urban heat islands and other areas affected by extreme temperatures due to climate change, as discussed by Christopher K. Uejio, PhD, from Florida State University in Tallahassee.
Air pollution expert George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the session, said that the PM2.5 standard includes nontoxic particulate matter, such as soil, and misses sub-micron sized particles, and asked Mr. Haynes whether smaller particles were being measured in the studies he described.
Mr. Haynes replied that the systems do not directly measure PM2.5 but instead rely on aerosol optical depth, a measure of the extent to which atmospheric particles absorb or scatter sunlight.
Dr. Thurston, who in 1987 was coauthor of groundbreaking study showing the link between PM2.5 levels and mortality, is now an advocate for a tougher standard of measuring ambient ultrafine particles with an aerodynamic diameter less than .1 microns in size (PM1).
NASA health and climate data are available at https://www.earthdata.nasa.gov/.
Mr. Haynes and Dr. Naeger are NASA employees. Dr. Thurston had no relevant disclosures.
FROM ATS 2024
New Administration Routes for Adrenaline in Anaphylaxis
PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.
Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).
One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.
“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
Anaphylaxis Incidence Increasing
Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.
Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.
While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.
Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.
“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
Adrenaline Treatment Criteria?
An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.
In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).
Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.
In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.
IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.
The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.
Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.
Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
Intranasal Adrenaline
To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.
Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.
A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.
In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.
However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.
A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.
In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.
Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.
In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
Sublingual Adrenaline Film
AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.
The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109 of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.
EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.
Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.
Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.
Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
Transcutaneous Adrenaline
A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.
Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.
Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).
One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.
“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
Anaphylaxis Incidence Increasing
Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.
Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.
While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.
Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.
“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
Adrenaline Treatment Criteria?
An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.
In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).
Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.
In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.
IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.
The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.
Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.
Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
Intranasal Adrenaline
To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.
Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.
A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.
In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.
However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.
A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.
In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.
Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.
In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
Sublingual Adrenaline Film
AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.
The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109 of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.
EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.
Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.
Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.
Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
Transcutaneous Adrenaline
A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.
Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
PARIS — While anaphylaxis requires immediate adrenaline administration through autoinjection, the use of this treatment is not optimal. Therefore, the development of new adrenaline formulations (such as for intranasal, sublingual, and transcutaneous routes) aims to facilitate the drug’s use and reduce persistent delays in administration by patients and caregivers. An overview of the research was presented at the 19th French-speaking Congress of Allergology.
Anaphylaxis is a severe and potentially fatal immediate hypersensitivity reaction with highly variable and dynamic clinical presentations. It requires prompt recognition for immediate treatment with intramuscular (IM) adrenaline (at the anterolateral aspect of the mid-thigh).
One might think that this reflex is acquired, but in France, while the number of prescribed adrenaline autoinjection (AAI) devices has been increasing for a decade, reaching 965,944 units in 2022, this first-line treatment is underused. Anapen (150, 300, and 500 µg), EpiPen (150 and 300 µg), Jext (150 µg and 300 µg), and Emerade (150, 300, and 500 µg) are the four products marketed in France in 2024.
“Only 17.3% of individuals presenting to the emergency department in the Lorraine region used it in 2015,” said Catherine Neukirch, MD, a pneumologist at Hôpital Bichat–Claude Bernard in Paris, France, with rates of 11.3% for children and 20.3% for adults.
Anaphylaxis Incidence Increasing
Approximately 0.3% (95% CI, 0.1-0.5) of the population will experience an anaphylaxis episode in their lifetime. Incidence in Europe, across all causes, is estimated between 1.5 and 7.9 cases per 100,000 inhabitants per year. Although anaphylaxis is on the rise, its associated mortality remains low, ranging between 0.05 and 0.51 per million per year for drugs, between 0.03 and 0.32 per million per year for foods, and between 0.09 and 0.13 per million per year for hymenopteran venoms.
Data from the European Anaphylaxis Registry indicate that anaphylaxis manifests rapidly after allergen exposure: 55% of cases occur within 10 minutes and 80% within 30 minutes. In addition, a biphasic reaction, which can occur up to 72 hours after exposure, is observed in < 5% of cases.
While a delay in adrenaline use is associated with risk for increased morbidity and mortality, AAI significantly reduces error rates compared with manual treatments involving ampoules, needles, and syringes. It also reduces the associated panic risks. However, there are multiple barriers to adrenaline use. The clinical symptoms of anaphylaxis may be misleading, especially if it occurs without cutaneous and urticarial manifestations but with only acute bronchospasm. It may present as isolated laryngeal edema without digestive involvement, hypotension, or other respiratory problems.
Other limitations to adrenaline use include technical difficulties and the possibility of incorrect administration, the need for appropriate needle sizes for patients with obesity, needle phobia, potential adverse effects of adrenaline injections, failure to carry two autoinjectors, constraints related to storage and bulky transport, as well as the need for training and practice.
“These factors contribute to underuse of adrenaline by patients and caregivers,” said Dr. Neukirch, which results in delays in necessary administration.
Adrenaline Treatment Criteria?
An analysis published in 2023 based on pharmacovigilance data from 30 regional French centers from 1984 to 2022 included 42 reported cases (average age, 33 years; 26% children) of reactions to AAI, which probably is an underestimate. About 40% of AAI uses occurred during anaphylaxis. The remaining 60% were triggered outside of reactions. The main reasons were accidental injections, mainly in the fingers, and cases of not triggering the autoinjector, underlining the importance of patient education.
In 2015, the European Medicines Agency required pharmacological studies for injectable adrenaline on healthy volunteers. These studies include ultrasound measurements of bolus injection, pharmacokinetics (ie, absorption, distribution, metabolism, and excretion), and pharmacodynamics (ie, the effect of the drug and the mechanism of action in the body), with precise evaluation of cardiovascular effects (eg, systolic and diastolic blood pressures and heart rate).
Among the information collected with the different products, ultrasound studies have shown a different localization of the adrenaline bolus (ie, in muscle in patients with normal BMI and mostly in adipose tissue in patients with BMI indicating overweight and obesity). The consequences of this finding are still unknown.
In a study with 500 µg Anapen, women with overweight or obesity showed different pharmacokinetic or pharmacodynamic profiles from those in men with normal weight, with an increase in the area under the curve (0-240 min) and marked changes in the heart rate time curve.
IM administration of 0.5 mg produces rapid pharmacokinetic effects in patients with normal weight, overweight, or obesity, with a delay for the second peak in the latter case. This delay perhaps results from initial local vasoconstriction due to adrenaline.
The early peak plasma concentration occurs at 5-10 minutes for AAI, with a faster speed for Anapen and EpiPen.
Moreover, needle size is not the most important factor. Rather, it is the strength and speed of injection, which can vary depending on the AAI.
Also, the optimal plasma concentration of adrenaline to treat anaphylaxis is not known; studies cannot be conducted during anaphylaxis. In terms of pharmacokinetics, a small series discovered that increased skin or muscle thickness delays the absorption of EpiPen AAI.
Intranasal Adrenaline
To facilitate rapid adrenaline use and convince reluctant patients to carry and use adrenaline, intranasal, sublingual, or transcutaneous forms are under development.
Three intranasal forms of adrenaline are already well advanced, including Neffy from ARS Pharma, epinephrine sprays from Bryn Pharma and Hikma, and Oxero from Oragoo, which contains dry powder.
A comparison of intranasal adrenaline Neffy and AAI shows that the former has satisfactory pharmacokinetic and pharmacodynamic effects.
In a phase 1 randomized crossover study of 42 healthy adults comparing the pharmacokinetic effects of Neffy adrenaline (2 mg) and EpiPen (0.3 mg), as well as IM epinephrine 0.3 mg, several observations were made. For a single dose, the maximum concentration (Cmax) of Neffy was lower than that of EpiPen.
However, with repeated doses administered 10 minutes apart, the Cmax of Neffy was higher than that of EpiPen. At this stage, pharmacodynamic responses to intranasal products are at least comparable with those of approved injectable products.
A comparison of the pharmacodynamic effects, such as systolic and diastolic blood pressures and heart rate, of Neffy adrenaline and AAI concluded that the profile of Neffy is comparable with that of EpiPen and superior to that of IM epinephrine.
In patients with a history of allergic rhinitis, adrenaline Cmax appears to be increased, while time to peak plasma concentration (Tmax) is reduced. Low blood pressure does not prevent Neffy absorption. Neffy is currently under review by the American and European health authorities.
Intranasal absorption of dry powder adrenaline appears to be faster than that of EpiPen, thus offering a clinical advantage in the short therapeutic window for anaphylaxis treatment.
In an open-label trial conducted on 12 adults with seasonal allergic rhinitis without asthma, the pharmacokinetics, pharmacodynamics, and safety of adrenaline were compared between FMXIN002 (1.6 and 3.2 mg), which was administered intranasally with or without nasal allergen challenge, and IM EpiPen 0.3 mg. Pharmacokinetics varied by patient. Nevertheless, nasal FMXIN002 had a shorter Tmax, a doubled Cmax after the allergen challenge peak, and a higher area under the curve in the 8 hours following administration compared with EpiPen. Pharmacodynamic effects comparable with those of EpiPen were noted at 15 minutes to 4 hours after administration. The tolerance was good, with mild and local side effects. The powder seems to deposit slightly better in the nasal cavity. It remains stable for 6 months at a temperature of 40 °C and relative humidity of 75% and for 2 years at a temperature of 25 °C and relative humidity of 60%.
Sublingual Adrenaline Film
AQST-109 is a sublingual film that is intended to allow rapid administration of epinephrine 1, which is a prodrug of adrenaline. The product is the size of a postage stamp, weighs < 30 g, and dissolves on contact with the tongue.
The EPIPHAST II study was a phase 1, multiperiod, crossover study conducted on 24 healthy adults (age, 24-49 years) who were randomly assigned to receive either 12 or 0.3 mg of AQST-109 of manual IM adrenaline in the first two periods. All participants received 0.3 mg of EpiPen in the last period.
EpiPen 0.3 mg resulted in a higher Cmax than AQST-109 12 mg. AQST-109 12 mg had the fastest median Tmax of 12 minutes. The areas under the curve of AQST-109 12 mg fell between those of EpiPen 0.3 mg and manual IM adrenaline 0.3 mg.
Early increases in systolic blood pressure, diastolic blood pressure, and heart rate were observed with AQST-109 12 mg. Changes were more pronounced with AQST-109 12 mg despite a higher Cmax with EpiPen 0.3 mg.
Part 3 of the EPIPHAST study evaluated the impact of food exposure (ie, a peanut butter sandwich) on the pharmacokinetics of AQST-109 12 mg in 24 healthy adults. Oral food residues did not significantly affect pharmacodynamic parameters, and no treatment-related adverse events were reported.
Researchers concluded that AQST-109 12 mg absorption would not be altered by “real” situations if used during meals. “These results suggest that the sublingual adrenaline film could be promising in real situations,” said Dr. Neukirch, especially in cases of food allergy with recent ingestion of the allergenic food.
Transcutaneous Adrenaline
A transcutaneous form of adrenaline that uses the Zeneo device developed by Crossject, a company based in Dijon, France, comes in the form of an AAI that requires no needle. This project, funded by the European Union, uses a gas generator to propel the drug at very high speed through the skin in 50 milliseconds. This method allows for extended drug storage.
Dr. Neukirch reported financial relationships with Viatris, Stallergènes, ALK, Astrazeneca, Sanofi, GSK, and Novartis.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Debate on pulmonary safety of gas stoves: Is the risk just hot air?
SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO2) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.
The debate was held at the American Thoracic Society’s international conference.
PRO: Gas stoves cause lung disease
Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”
Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO2 with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.
“We know that NO2 is an irritant gas that can cause bronchoconstriction, airway hyperresponsiveness and inflammation, and there’s increased risk of asthma and COPD exacerbations,” he said.
The US Environmental Protection Agency (EPA) outdoor ambient air standard for NO2 is 100 parts per billion (ppb) or lower, which are the levels needed to prevent asthma exacerbations. In separate meta-analyses there was a 1.05 rise in asthma incidence per every 2 ppb of NO2, and an increase of 1.07 in COPD incidence for every 5 ppb of NO2, Dr. Balmes noted.
The respiratory effects of gas stoves were revealed in a 2013 meta-analysis of 10 studies from North America and Europe, which showed a pooled odds ratio for current asthma of 1.34. Building on these data, authors of a 2022 paper estimated that 13% of childhood asthma could be prevented by elimination gas cooking.
Although the causative link is missing, the evidence is abundant that natural gas isn’t good for anyone, he acknowledged.
Con: More evidence needed
Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”
But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).
The link between gas and risk of asthma was significant only for adults, however, and the data on the risks for COPD and for pneumonia or other respiratory infections came almost exclusively from low-income countries, she noted.
Despite the lack of evidence for a causative link, however, Dr. McCormack pointed to evidence that indoor NO2 is an air pollutant that acts as a respiratory irritant, and that indoor NO2 levels in homes with gas stoves have been shown to be more than twice as high as those in homes with electric stoves.
Other evidence shows that indoor NO2 is associated with increased symptoms and use of rescue medications for children with asthma, and with shortness of breath, nocturnal symptoms, reduction in lung function, and exacerbations in COPD.
Still other studies have shown that exchanging a gas stove for an electric stove can reduce NO2 concentrations in the home by up to 50%, but there is still a need for clinical trial evidence of a health benefit for such an exchange, she said.
And even if a gas stove is swapped out for an electric or induction range, household members with asthma are exposed to other hazards, including second-hand smoke, cooking exhaust, candle or incense burning, outdoor particulate matter that finds its way indoors, mold, and mouse or cockroach allergens, she noted.
On common ground
Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.
Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.
“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
End indoor combustion
George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO2 but didn’t touch on particulate pollution generated by gas stoves.
Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.
“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.
Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.
SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO2) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.
The debate was held at the American Thoracic Society’s international conference.
PRO: Gas stoves cause lung disease
Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”
Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO2 with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.
“We know that NO2 is an irritant gas that can cause bronchoconstriction, airway hyperresponsiveness and inflammation, and there’s increased risk of asthma and COPD exacerbations,” he said.
The US Environmental Protection Agency (EPA) outdoor ambient air standard for NO2 is 100 parts per billion (ppb) or lower, which are the levels needed to prevent asthma exacerbations. In separate meta-analyses there was a 1.05 rise in asthma incidence per every 2 ppb of NO2, and an increase of 1.07 in COPD incidence for every 5 ppb of NO2, Dr. Balmes noted.
The respiratory effects of gas stoves were revealed in a 2013 meta-analysis of 10 studies from North America and Europe, which showed a pooled odds ratio for current asthma of 1.34. Building on these data, authors of a 2022 paper estimated that 13% of childhood asthma could be prevented by elimination gas cooking.
Although the causative link is missing, the evidence is abundant that natural gas isn’t good for anyone, he acknowledged.
Con: More evidence needed
Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”
But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).
The link between gas and risk of asthma was significant only for adults, however, and the data on the risks for COPD and for pneumonia or other respiratory infections came almost exclusively from low-income countries, she noted.
Despite the lack of evidence for a causative link, however, Dr. McCormack pointed to evidence that indoor NO2 is an air pollutant that acts as a respiratory irritant, and that indoor NO2 levels in homes with gas stoves have been shown to be more than twice as high as those in homes with electric stoves.
Other evidence shows that indoor NO2 is associated with increased symptoms and use of rescue medications for children with asthma, and with shortness of breath, nocturnal symptoms, reduction in lung function, and exacerbations in COPD.
Still other studies have shown that exchanging a gas stove for an electric stove can reduce NO2 concentrations in the home by up to 50%, but there is still a need for clinical trial evidence of a health benefit for such an exchange, she said.
And even if a gas stove is swapped out for an electric or induction range, household members with asthma are exposed to other hazards, including second-hand smoke, cooking exhaust, candle or incense burning, outdoor particulate matter that finds its way indoors, mold, and mouse or cockroach allergens, she noted.
On common ground
Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.
Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.
“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
End indoor combustion
George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO2 but didn’t touch on particulate pollution generated by gas stoves.
Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.
“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.
Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.
SAN DIEGO — While there is currently no smoking gun definitively showing that indoor nitrogen dioxide (NO2) concentrations from gas appliances are a cause of pulmonary diseases, the circumstantial evidence of the baleful effects of gas stoves on lung function is pretty compelling, said participants in a pro-con debate.
The debate was held at the American Thoracic Society’s international conference.
PRO: Gas stoves cause lung disease
Arguing for the “pro” side, John R. Balmes, MD of the University of California, San Francisco, and a physician member of the California Air Resources Board, began by admitting that “I would never have said gas stoves cause lung disease, but that’s what they assigned me.”
Gamely proceeding anyway, Dr. Balmes noted that natural gas — methane — is a potent greenhouse gas, and that cooking with natural gas leads to generation of NO2 with high peak concentrations in the home, especially in the kitchen, but in other rooms as well.
“We know that NO2 is an irritant gas that can cause bronchoconstriction, airway hyperresponsiveness and inflammation, and there’s increased risk of asthma and COPD exacerbations,” he said.
The US Environmental Protection Agency (EPA) outdoor ambient air standard for NO2 is 100 parts per billion (ppb) or lower, which are the levels needed to prevent asthma exacerbations. In separate meta-analyses there was a 1.05 rise in asthma incidence per every 2 ppb of NO2, and an increase of 1.07 in COPD incidence for every 5 ppb of NO2, Dr. Balmes noted.
The respiratory effects of gas stoves were revealed in a 2013 meta-analysis of 10 studies from North America and Europe, which showed a pooled odds ratio for current asthma of 1.34. Building on these data, authors of a 2022 paper estimated that 13% of childhood asthma could be prevented by elimination gas cooking.
Although the causative link is missing, the evidence is abundant that natural gas isn’t good for anyone, he acknowledged.
Con: More evidence needed
Arguing for the “con” side of the question, Meredith C. McCormack, MD, MHS, professor of medicine in the pulmonary and critical care division at Johns Hopkins University in Baltimore, said that “more definitive evidence is needed to define whether gas stoves cause lung disease.”
But Dr. McCormack didn’t let the natural gas industry off the hook, noting that a systematic review and meta-analysis of cooking with gas in high-, middle-, and low-income countries showed that domestic use of gas fuels vs. electric was associated with increased risk of asthma (1.11 overall), COPD (1.15), and pneumonia (1.26).
The link between gas and risk of asthma was significant only for adults, however, and the data on the risks for COPD and for pneumonia or other respiratory infections came almost exclusively from low-income countries, she noted.
Despite the lack of evidence for a causative link, however, Dr. McCormack pointed to evidence that indoor NO2 is an air pollutant that acts as a respiratory irritant, and that indoor NO2 levels in homes with gas stoves have been shown to be more than twice as high as those in homes with electric stoves.
Other evidence shows that indoor NO2 is associated with increased symptoms and use of rescue medications for children with asthma, and with shortness of breath, nocturnal symptoms, reduction in lung function, and exacerbations in COPD.
Still other studies have shown that exchanging a gas stove for an electric stove can reduce NO2 concentrations in the home by up to 50%, but there is still a need for clinical trial evidence of a health benefit for such an exchange, she said.
And even if a gas stove is swapped out for an electric or induction range, household members with asthma are exposed to other hazards, including second-hand smoke, cooking exhaust, candle or incense burning, outdoor particulate matter that finds its way indoors, mold, and mouse or cockroach allergens, she noted.
On common ground
Environmental interventions that can benefit all members of a household — not just those with obstructive pulmonary disease — include smoking cessation, charcoal filter-equipped air cleaners, stove hoods that vent outdoors, integrated pest management, hypoallergenic pillow and mattress covers, high efficiency particulate air (HEPA) vacuums, and mold and radon abatement.
Both Dr. Balmes and Dr. McCormack agreed in the end that gas stoves contribute to respiratory morbidity, and that both state and national policy changes are needed to support transition to cleaner indoor air, with financial incentives available for households with more modest incomes.
“For everyone, there is a climate-change mitigation imperative to transition away from gas appliances if we want to tackle the climate emergency,” Dr. Balmes said.
End indoor combustion
George D. Thurston, ScD, professor of medicine and population health at the NYU Grossman School of Medicine, who attended the debate, told Chest Physician that the participants talked about NO2 but didn’t touch on particulate pollution generated by gas stoves.
Burning natural gas produces particles that are very similar in composition to those produced by burning coal, oil, or diesel fuel, Dr. Thurston said, and he pointed out that interventions such as range hoods work only if they actually vent outdoors, and aren’t simply fans that recirculate the air within the home. And even when ventilation works as it should to move air out of the house, it only pumps it back into the atmosphere, where it contributes to climate change.
“We need combustion-free homes. That’s the unifying principle. We have to keep our eyes on that prize,” he said.
Dr. Balmes, Dr. McCormack, and Dr. Thurston all reported having no relevant disclosures.
FROM ATS 2024