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Is air filtration the best public health intervention against respiratory viruses?
This transcript has been edited for clarity.
When it comes to the public health fight against respiratory viruses – COVID, flu, RSV, and so on – it has always struck me as strange how staunchly basically any intervention is opposed. Masking was, of course, the prototypical entrenched warfare of opposing ideologies, with advocates pointing to studies suggesting the efficacy of masking to prevent transmission and advocating for broad masking recommendations, and detractors citing studies that suggested masks were ineffective and characterizing masking policies as fascist overreach. I’ll admit that I was always perplexed by this a bit, as that particular intervention seemed so benign – a bit annoying, I guess, but not crazy.
I have come to appreciate what I call status quo bias, which is the tendency to reject any policy, advice, or intervention that would force you, as an individual, to change your usual behavior. We just don’t like to do that. It has made me think that the most successful public health interventions might be the ones that take the individual out of the loop. And air quality control seems an ideal fit here. Here is a potential intervention where you, the individual, have to do precisely nothing. The status quo is preserved. We just, you know, have cleaner indoor air.
But even the suggestion of air treatment systems as a bulwark against respiratory virus transmission has been met with not just skepticism but cynicism, and perhaps even defeatism. It seems that there are those out there who think there really is nothing we can do. Sickness is interpreted in a Calvinistic framework: You become ill because it is your pre-destiny. But maybe air treatment could actually work. It seems like it might, if a new paper from PLOS One is to be believed.
What we’re talking about is a study titled “Bipolar Ionization Rapidly Inactivates Real-World, Airborne Concentrations of Infective Respiratory Viruses” – a highly controlled, laboratory-based analysis of a bipolar ionization system which seems to rapidly reduce viral counts in the air.
The proposed mechanism of action is pretty simple. The ionization system – which, don’t worry, has been shown not to produce ozone – spits out positively and negatively charged particles, which float around the test chamber, designed to look like a pretty standard room that you might find in an office or a school.
Virus is then injected into the chamber through an aerosolization machine, to achieve concentrations on the order of what you might get standing within 6 feet or so of someone actively infected with COVID while they are breathing and talking.
The idea is that those ions stick to the virus particles, similar to how a balloon sticks to the wall after you rub it on your hair, and that tends to cause them to clump together and settle on surfaces more rapidly, and thus get farther away from their ports of entry to the human system: nose, mouth, and eyes. But the ions may also interfere with viruses’ ability to bind to cellular receptors, even in the air.
To quantify viral infectivity, the researchers used a biological system. Basically, you take air samples and expose a petri dish of cells to them and see how many cells die. Fewer cells dying, less infective. Under control conditions, you can see that virus infectivity does decrease over time. Time zero here is the end of a SARS-CoV-2 aerosolization.
This may simply reflect the fact that virus particles settle out of the air. But As you can see, within about an hour, you have almost no infective virus detectable. That’s fairly impressive.
Now, I’m not saying that this is a panacea, but it is certainly worth considering the use of technologies like these if we are going to revamp the infrastructure of our offices and schools. And, of course, it would be nice to see this tested in a rigorous clinical trial with actual infected people, not cells, as the outcome. But I continue to be encouraged by interventions like this which, to be honest, ask very little of us as individuals. Maybe it’s time we accept the things, or people, that we cannot change.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
When it comes to the public health fight against respiratory viruses – COVID, flu, RSV, and so on – it has always struck me as strange how staunchly basically any intervention is opposed. Masking was, of course, the prototypical entrenched warfare of opposing ideologies, with advocates pointing to studies suggesting the efficacy of masking to prevent transmission and advocating for broad masking recommendations, and detractors citing studies that suggested masks were ineffective and characterizing masking policies as fascist overreach. I’ll admit that I was always perplexed by this a bit, as that particular intervention seemed so benign – a bit annoying, I guess, but not crazy.
I have come to appreciate what I call status quo bias, which is the tendency to reject any policy, advice, or intervention that would force you, as an individual, to change your usual behavior. We just don’t like to do that. It has made me think that the most successful public health interventions might be the ones that take the individual out of the loop. And air quality control seems an ideal fit here. Here is a potential intervention where you, the individual, have to do precisely nothing. The status quo is preserved. We just, you know, have cleaner indoor air.
But even the suggestion of air treatment systems as a bulwark against respiratory virus transmission has been met with not just skepticism but cynicism, and perhaps even defeatism. It seems that there are those out there who think there really is nothing we can do. Sickness is interpreted in a Calvinistic framework: You become ill because it is your pre-destiny. But maybe air treatment could actually work. It seems like it might, if a new paper from PLOS One is to be believed.
What we’re talking about is a study titled “Bipolar Ionization Rapidly Inactivates Real-World, Airborne Concentrations of Infective Respiratory Viruses” – a highly controlled, laboratory-based analysis of a bipolar ionization system which seems to rapidly reduce viral counts in the air.
The proposed mechanism of action is pretty simple. The ionization system – which, don’t worry, has been shown not to produce ozone – spits out positively and negatively charged particles, which float around the test chamber, designed to look like a pretty standard room that you might find in an office or a school.
Virus is then injected into the chamber through an aerosolization machine, to achieve concentrations on the order of what you might get standing within 6 feet or so of someone actively infected with COVID while they are breathing and talking.
The idea is that those ions stick to the virus particles, similar to how a balloon sticks to the wall after you rub it on your hair, and that tends to cause them to clump together and settle on surfaces more rapidly, and thus get farther away from their ports of entry to the human system: nose, mouth, and eyes. But the ions may also interfere with viruses’ ability to bind to cellular receptors, even in the air.
To quantify viral infectivity, the researchers used a biological system. Basically, you take air samples and expose a petri dish of cells to them and see how many cells die. Fewer cells dying, less infective. Under control conditions, you can see that virus infectivity does decrease over time. Time zero here is the end of a SARS-CoV-2 aerosolization.
This may simply reflect the fact that virus particles settle out of the air. But As you can see, within about an hour, you have almost no infective virus detectable. That’s fairly impressive.
Now, I’m not saying that this is a panacea, but it is certainly worth considering the use of technologies like these if we are going to revamp the infrastructure of our offices and schools. And, of course, it would be nice to see this tested in a rigorous clinical trial with actual infected people, not cells, as the outcome. But I continue to be encouraged by interventions like this which, to be honest, ask very little of us as individuals. Maybe it’s time we accept the things, or people, that we cannot change.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
When it comes to the public health fight against respiratory viruses – COVID, flu, RSV, and so on – it has always struck me as strange how staunchly basically any intervention is opposed. Masking was, of course, the prototypical entrenched warfare of opposing ideologies, with advocates pointing to studies suggesting the efficacy of masking to prevent transmission and advocating for broad masking recommendations, and detractors citing studies that suggested masks were ineffective and characterizing masking policies as fascist overreach. I’ll admit that I was always perplexed by this a bit, as that particular intervention seemed so benign – a bit annoying, I guess, but not crazy.
I have come to appreciate what I call status quo bias, which is the tendency to reject any policy, advice, or intervention that would force you, as an individual, to change your usual behavior. We just don’t like to do that. It has made me think that the most successful public health interventions might be the ones that take the individual out of the loop. And air quality control seems an ideal fit here. Here is a potential intervention where you, the individual, have to do precisely nothing. The status quo is preserved. We just, you know, have cleaner indoor air.
But even the suggestion of air treatment systems as a bulwark against respiratory virus transmission has been met with not just skepticism but cynicism, and perhaps even defeatism. It seems that there are those out there who think there really is nothing we can do. Sickness is interpreted in a Calvinistic framework: You become ill because it is your pre-destiny. But maybe air treatment could actually work. It seems like it might, if a new paper from PLOS One is to be believed.
What we’re talking about is a study titled “Bipolar Ionization Rapidly Inactivates Real-World, Airborne Concentrations of Infective Respiratory Viruses” – a highly controlled, laboratory-based analysis of a bipolar ionization system which seems to rapidly reduce viral counts in the air.
The proposed mechanism of action is pretty simple. The ionization system – which, don’t worry, has been shown not to produce ozone – spits out positively and negatively charged particles, which float around the test chamber, designed to look like a pretty standard room that you might find in an office or a school.
Virus is then injected into the chamber through an aerosolization machine, to achieve concentrations on the order of what you might get standing within 6 feet or so of someone actively infected with COVID while they are breathing and talking.
The idea is that those ions stick to the virus particles, similar to how a balloon sticks to the wall after you rub it on your hair, and that tends to cause them to clump together and settle on surfaces more rapidly, and thus get farther away from their ports of entry to the human system: nose, mouth, and eyes. But the ions may also interfere with viruses’ ability to bind to cellular receptors, even in the air.
To quantify viral infectivity, the researchers used a biological system. Basically, you take air samples and expose a petri dish of cells to them and see how many cells die. Fewer cells dying, less infective. Under control conditions, you can see that virus infectivity does decrease over time. Time zero here is the end of a SARS-CoV-2 aerosolization.
This may simply reflect the fact that virus particles settle out of the air. But As you can see, within about an hour, you have almost no infective virus detectable. That’s fairly impressive.
Now, I’m not saying that this is a panacea, but it is certainly worth considering the use of technologies like these if we are going to revamp the infrastructure of our offices and schools. And, of course, it would be nice to see this tested in a rigorous clinical trial with actual infected people, not cells, as the outcome. But I continue to be encouraged by interventions like this which, to be honest, ask very little of us as individuals. Maybe it’s time we accept the things, or people, that we cannot change.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Intense exercise may lead to colds. A new study tells us why
Can too much of a healthy habit become bad?
Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, according to a new study.
The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be).
Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.
But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.
“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”
That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel.
The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear.
After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts.
“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
An adaptive mechanism gone awry
During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.
Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”
The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.
But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
Advice for patients
More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said.
As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.
“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.
And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
A version of this article first appeared on Medscape.com.
Can too much of a healthy habit become bad?
Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, according to a new study.
The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be).
Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.
But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.
“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”
That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel.
The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear.
After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts.
“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
An adaptive mechanism gone awry
During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.
Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”
The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.
But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
Advice for patients
More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said.
As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.
“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.
And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
A version of this article first appeared on Medscape.com.
Can too much of a healthy habit become bad?
Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, according to a new study.
The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be).
Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.
But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.
“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”
That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel.
The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear.
After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts.
“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
An adaptive mechanism gone awry
During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.
Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”
The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.
But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
Advice for patients
More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said.
As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.
“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.
And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
A version of this article first appeared on Medscape.com.
FROM MILITARY MEDICAL RESEARCH
Pulmonary aspergillosis predicts poor outcomes in critically ill flu patients
Critically ill influenza patients with associated pulmonary aspergillosis were more than twice as likely to die in intensive care than those without the added infection, based on data from a meta-analysis of more than 1,700 individuals.
Reports of influenza-associated pulmonary aspergillosis (IAPA) are rising in critically ill patients, but data on risk factors, clinical features, and outcomes are limited, Lawrence Y. Lu, MD, of The Prince Charles Hospital, Brisbane, Australia, and colleagues wrote. In addition, diagnosis of IAPA can be challenging, and many clinicians report low awareness of the condition.
In a study published in the journal Chest, the researchers reviewed data from 10 observational studies including 1,720 critically ill influenza patients aged 16 years and older; of these, 331 had IAPA, for a prevalence of 19.2%. The primary outcomes were all-cause mortality in the hospital and in the ICU. Secondary outcomes included ICU length of stay, hospital length of stay, and the need for supportive care (invasive and noninvasive mechanical ventilation, renal replacement therapy, pressor support, and extracorporeal membranous oxygenation).
Overall, mortality among flu patients in the ICU was significantly higher for those with IAPA than those without IAPA (45.0% vs. 23.8%, respectively), as was all-cause mortality (46.4% vs. 26.2%, respectively; odds ratio, 2.6 and P < .001 for both ICU and all-cause mortality).
Factors significantly associated with an increased risk for IAPA included organ transplant (OR, 4.8), hematogenous malignancy (OR, 2.5), being immunocompromised in some way (OR, 2.2), and prolonged corticosteroid use prior to hospital admission (OR, 2.4).
IAPA also was associated with more severe disease, a higher rate of complications, longer ICU stays, and a greater need for organ supports, the researchers noted. Clinical features not significantly more common in patients with IAPA included fever, hemoptysis, and acute respiratory distress syndrome.
The findings were limited by several factors including the retrospective design of the included studies and inability to control for all potential confounders, the researchers noted. Other limitations included the variations in study design, variability of practice patterns across locations, and inclusion of data mainly from countries of high socioeconomic status.
“Given the apparent waning of the COVID-19 pandemic and re-emergence of influenza, our analysis also revealed other gaps in the current literature, including the need to validate newer diagnostic methods and to develop a system to measure severity of IAPA,” the researchers added.
However, the current study results reflect IAPA prevalence from previous studies, and support the need to have a lower threshold for IAPA testing and initiation of antifungal treatment, even with limited data for clinical guidance, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Critically ill influenza patients with associated pulmonary aspergillosis were more than twice as likely to die in intensive care than those without the added infection, based on data from a meta-analysis of more than 1,700 individuals.
Reports of influenza-associated pulmonary aspergillosis (IAPA) are rising in critically ill patients, but data on risk factors, clinical features, and outcomes are limited, Lawrence Y. Lu, MD, of The Prince Charles Hospital, Brisbane, Australia, and colleagues wrote. In addition, diagnosis of IAPA can be challenging, and many clinicians report low awareness of the condition.
In a study published in the journal Chest, the researchers reviewed data from 10 observational studies including 1,720 critically ill influenza patients aged 16 years and older; of these, 331 had IAPA, for a prevalence of 19.2%. The primary outcomes were all-cause mortality in the hospital and in the ICU. Secondary outcomes included ICU length of stay, hospital length of stay, and the need for supportive care (invasive and noninvasive mechanical ventilation, renal replacement therapy, pressor support, and extracorporeal membranous oxygenation).
Overall, mortality among flu patients in the ICU was significantly higher for those with IAPA than those without IAPA (45.0% vs. 23.8%, respectively), as was all-cause mortality (46.4% vs. 26.2%, respectively; odds ratio, 2.6 and P < .001 for both ICU and all-cause mortality).
Factors significantly associated with an increased risk for IAPA included organ transplant (OR, 4.8), hematogenous malignancy (OR, 2.5), being immunocompromised in some way (OR, 2.2), and prolonged corticosteroid use prior to hospital admission (OR, 2.4).
IAPA also was associated with more severe disease, a higher rate of complications, longer ICU stays, and a greater need for organ supports, the researchers noted. Clinical features not significantly more common in patients with IAPA included fever, hemoptysis, and acute respiratory distress syndrome.
The findings were limited by several factors including the retrospective design of the included studies and inability to control for all potential confounders, the researchers noted. Other limitations included the variations in study design, variability of practice patterns across locations, and inclusion of data mainly from countries of high socioeconomic status.
“Given the apparent waning of the COVID-19 pandemic and re-emergence of influenza, our analysis also revealed other gaps in the current literature, including the need to validate newer diagnostic methods and to develop a system to measure severity of IAPA,” the researchers added.
However, the current study results reflect IAPA prevalence from previous studies, and support the need to have a lower threshold for IAPA testing and initiation of antifungal treatment, even with limited data for clinical guidance, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Critically ill influenza patients with associated pulmonary aspergillosis were more than twice as likely to die in intensive care than those without the added infection, based on data from a meta-analysis of more than 1,700 individuals.
Reports of influenza-associated pulmonary aspergillosis (IAPA) are rising in critically ill patients, but data on risk factors, clinical features, and outcomes are limited, Lawrence Y. Lu, MD, of The Prince Charles Hospital, Brisbane, Australia, and colleagues wrote. In addition, diagnosis of IAPA can be challenging, and many clinicians report low awareness of the condition.
In a study published in the journal Chest, the researchers reviewed data from 10 observational studies including 1,720 critically ill influenza patients aged 16 years and older; of these, 331 had IAPA, for a prevalence of 19.2%. The primary outcomes were all-cause mortality in the hospital and in the ICU. Secondary outcomes included ICU length of stay, hospital length of stay, and the need for supportive care (invasive and noninvasive mechanical ventilation, renal replacement therapy, pressor support, and extracorporeal membranous oxygenation).
Overall, mortality among flu patients in the ICU was significantly higher for those with IAPA than those without IAPA (45.0% vs. 23.8%, respectively), as was all-cause mortality (46.4% vs. 26.2%, respectively; odds ratio, 2.6 and P < .001 for both ICU and all-cause mortality).
Factors significantly associated with an increased risk for IAPA included organ transplant (OR, 4.8), hematogenous malignancy (OR, 2.5), being immunocompromised in some way (OR, 2.2), and prolonged corticosteroid use prior to hospital admission (OR, 2.4).
IAPA also was associated with more severe disease, a higher rate of complications, longer ICU stays, and a greater need for organ supports, the researchers noted. Clinical features not significantly more common in patients with IAPA included fever, hemoptysis, and acute respiratory distress syndrome.
The findings were limited by several factors including the retrospective design of the included studies and inability to control for all potential confounders, the researchers noted. Other limitations included the variations in study design, variability of practice patterns across locations, and inclusion of data mainly from countries of high socioeconomic status.
“Given the apparent waning of the COVID-19 pandemic and re-emergence of influenza, our analysis also revealed other gaps in the current literature, including the need to validate newer diagnostic methods and to develop a system to measure severity of IAPA,” the researchers added.
However, the current study results reflect IAPA prevalence from previous studies, and support the need to have a lower threshold for IAPA testing and initiation of antifungal treatment, even with limited data for clinical guidance, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL CHEST
Pandemic blamed for failed trial of inhaled antibiotic
NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.
“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.
The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.
The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.
Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.
The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.
On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).
With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.
Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.
There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.
While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” obscuring a benefit that would have been otherwise shown.
Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.
Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”
If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.
Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.
Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”
Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.
“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.
Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.
“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.
The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.
The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.
Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.
The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.
On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).
With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.
Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.
There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.
While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” obscuring a benefit that would have been otherwise shown.
Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.
Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”
If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.
Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.
Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”
Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.
“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.
Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.
“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.
The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.
The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.
Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.
The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.
On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).
With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.
Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.
There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.
While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” obscuring a benefit that would have been otherwise shown.
Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.
Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”
If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.
Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.
Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”
Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.
“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.
Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM WBC 2023
Neutropenia affects clinical presentation of pulmonary mucormycosis
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
FROM THE JOURNAL CHEST
Does screening kids with acute sinusitis symptoms for bacterial infection cut unnecessary antibiotic use?
Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.
The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.
If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.
Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.
“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”
Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.
“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.
In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).
For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.
In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).
Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).
The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
Welcome findings
Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”
Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.
“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.
The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.
“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”
Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.
All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.
A version of this article first appeared on Medscape.com.
Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.
The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.
If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.
Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.
“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”
Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.
“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.
In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).
For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.
In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).
Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).
The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
Welcome findings
Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”
Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.
“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.
The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.
“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”
Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.
All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.
A version of this article first appeared on Medscape.com.
Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.
The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.
If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.
Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.
“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”
Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.
“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.
In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).
For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.
In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).
Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).
The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
Welcome findings
Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”
Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.
“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.
The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.
“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”
Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.
All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.
A version of this article first appeared on Medscape.com.
FROM JAMA
Fungal cultures in bronchiectasis don’t predict outcomes
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
Asthma severity, exacerbations increase with RV infection
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
Nebulized amphotericin B does not affect aspergillosis exacerbation-free status at 1 year
Topline
Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.
Methodology
Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.
They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.
The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
Takeaway
From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).
The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.
Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).
The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
In practice
Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”
Study details
“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.
Limitations
The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.
Methodology
Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.
They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.
The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
Takeaway
From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).
The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.
Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).
The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
In practice
Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”
Study details
“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.
Limitations
The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.
Methodology
Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.
They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.
The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
Takeaway
From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).
The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.
Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).
The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
In practice
Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”
Study details
“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.
Limitations
The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.
A version of this article originally appeared on Medscape.com.
Comorbid respiratory disease key predictor of NTM-PD
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.