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Diagnosing progressive pulmonary fibrosis
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
AT ERS 2023
Minimally invasive surfactant shows some benefit in infants’ first 2 years
Results of the OPTIMIST follow-up study were published online in JAMA.
Researchers, led by Peter A. Dargaville, MD, department of paediatrics, Royal Hobart (Australia) Hospital, found that MIST, which involves administering surfactant via a thin catheter, compared with sham treatment, did not reduce the incidence of death or neurodevelopmental disability (NDD) by 2 years of age.
However, infants who received MIST had lower rates of poor respiratory outcomes during those first 2 years of life.
Study spanned 11 countries
The study was conducted in 33 tertiary neonatal intensive care units (NICUs) in 11 countries, including Australia, Canada, Israel, New Zealand, Qatar, Singapore, Slovenia, the Netherlands, Turkey, the United Kingdom, and the United States.
It included 486 infants 25-28 weeks old supported with CPAP; 453 had follow-up data available and data on the key secondary outcome were available for 434 infants.
The sham treatment consisted of only transient repositioning without airway instruments. Treating clinicians, outcome assessors, and parents were blinded to group status.
No significant difference in deaths, NDD
Death or NDD occurred in 36.3% of the patients in the MIST group and 36.1% in the control group (risk difference, 0%; 95% confidence interval, −7.6% to 7.7%; relative risk, 1.0; 95% confidence interval, 0.81-1.24).
Secondary respiratory outcomes were better in the MIST group:
- Hospitalization with respiratory illness occurred in 25.1% in the MIST group versus 38.2% in the control group (RR, 0.66; 95% CI, 0.54-0.81).
- Parent-reported wheezing or breathing difficulty occurred in 40.6% in the MIST group versus 53.6% in controls (RR, 0.76; 95% CI, 0.63-0.90).
- Asthma diagnosed by a physician was reported in 4.4% and 11.9% of MIST and control-group infants, respectively.
- Reported use of inhaled relievers (beta2 agonists) was 23.9% in the MIST group versus 38.7% in controls.
The previous study of early outcomes of deaths or bronchopulmonary dysplasia (BPD; chronic lung injury in preterm infants) was published by the same group of researchers in 2021.
Important benefit for respiratory health
Suhas G. Kallapur, MD, chief of the divisions of neonatology and developmental biology at University of California, Los Angeles, who was not part of either study, said: “This is one of the largest studies to date examining whether the MIST procedure for surfactant is beneficial in preterm babies born at 25-28 weeks’ gestation.”
Overall, when considering the 2021 and 2023 studies together, it appears that the MIST therapy has important benefits for respiratory health during a NICU stay and in early infancy, even though the primary outcome of death or NDD was not different between the treatment and control groups, Dr. Kallapur said.
“The slight (nonsignificant) increase in deaths in the MIST group was confined to the more immature babies – 25-26 weeks’ gestation at birth,” he pointed out. “In the bigger and more mature babies – 27-28 week gestation infants – the benefits of MIST therapy occurred without any increase in mortality, suggesting that this group of babies may be the group that stands to benefit most from this therapy.”
Dr. Kallapur said new data in the developmental origins of health and disease “now show that the trajectory of respiratory health in infancy is an important determinant of respiratory health into adulthood and older age.”
Therefore, the finding of benefit to respiratory health is particularly important, he said.
He noted that MIST or similar therapy is already in use in many NICUs throughout the world and that those already using it will likely feel vindicated by this study.
“Neonatologists who were on the sidelines will likely see these results – especially childhood respiratory outcomes – as a reason to initiate this procedure in all but the most immature preterm infants,” Dr. Kallapur says.
Dr. Dargaville reports personal fees from AbbVie and Chiesi Farmaceutici and provision of surfactant at reduced cost and support for conference travel from Chiesi Farmaceutici during the conduct of the study; in addition, Dr. Dargaville has been issued a patent for a catheter design. One coauthor reports grants from Chiesi Farmaceutici during the conduct of the study. Another coauthor reports serving as chief investigator for OPTI-SURF, an observational study on United Kingdom neonatal surfactant use in respiratory distress syndrome funded by Chiesi UK outside the submitted work. A third coauthor reports personal fees from Chiesi Farmaceutici outside the submitted work. This study was funded by grants from the Royal Hobart Hospital Research Foundation and the Australian National Health and Medical Research Council. Exogenous surfactant was provided at reduced cost by Chiesi Farmaceutici. Dr. Kallapur has no relevant financial relationships.
Results of the OPTIMIST follow-up study were published online in JAMA.
Researchers, led by Peter A. Dargaville, MD, department of paediatrics, Royal Hobart (Australia) Hospital, found that MIST, which involves administering surfactant via a thin catheter, compared with sham treatment, did not reduce the incidence of death or neurodevelopmental disability (NDD) by 2 years of age.
However, infants who received MIST had lower rates of poor respiratory outcomes during those first 2 years of life.
Study spanned 11 countries
The study was conducted in 33 tertiary neonatal intensive care units (NICUs) in 11 countries, including Australia, Canada, Israel, New Zealand, Qatar, Singapore, Slovenia, the Netherlands, Turkey, the United Kingdom, and the United States.
It included 486 infants 25-28 weeks old supported with CPAP; 453 had follow-up data available and data on the key secondary outcome were available for 434 infants.
The sham treatment consisted of only transient repositioning without airway instruments. Treating clinicians, outcome assessors, and parents were blinded to group status.
No significant difference in deaths, NDD
Death or NDD occurred in 36.3% of the patients in the MIST group and 36.1% in the control group (risk difference, 0%; 95% confidence interval, −7.6% to 7.7%; relative risk, 1.0; 95% confidence interval, 0.81-1.24).
Secondary respiratory outcomes were better in the MIST group:
- Hospitalization with respiratory illness occurred in 25.1% in the MIST group versus 38.2% in the control group (RR, 0.66; 95% CI, 0.54-0.81).
- Parent-reported wheezing or breathing difficulty occurred in 40.6% in the MIST group versus 53.6% in controls (RR, 0.76; 95% CI, 0.63-0.90).
- Asthma diagnosed by a physician was reported in 4.4% and 11.9% of MIST and control-group infants, respectively.
- Reported use of inhaled relievers (beta2 agonists) was 23.9% in the MIST group versus 38.7% in controls.
The previous study of early outcomes of deaths or bronchopulmonary dysplasia (BPD; chronic lung injury in preterm infants) was published by the same group of researchers in 2021.
Important benefit for respiratory health
Suhas G. Kallapur, MD, chief of the divisions of neonatology and developmental biology at University of California, Los Angeles, who was not part of either study, said: “This is one of the largest studies to date examining whether the MIST procedure for surfactant is beneficial in preterm babies born at 25-28 weeks’ gestation.”
Overall, when considering the 2021 and 2023 studies together, it appears that the MIST therapy has important benefits for respiratory health during a NICU stay and in early infancy, even though the primary outcome of death or NDD was not different between the treatment and control groups, Dr. Kallapur said.
“The slight (nonsignificant) increase in deaths in the MIST group was confined to the more immature babies – 25-26 weeks’ gestation at birth,” he pointed out. “In the bigger and more mature babies – 27-28 week gestation infants – the benefits of MIST therapy occurred without any increase in mortality, suggesting that this group of babies may be the group that stands to benefit most from this therapy.”
Dr. Kallapur said new data in the developmental origins of health and disease “now show that the trajectory of respiratory health in infancy is an important determinant of respiratory health into adulthood and older age.”
Therefore, the finding of benefit to respiratory health is particularly important, he said.
He noted that MIST or similar therapy is already in use in many NICUs throughout the world and that those already using it will likely feel vindicated by this study.
“Neonatologists who were on the sidelines will likely see these results – especially childhood respiratory outcomes – as a reason to initiate this procedure in all but the most immature preterm infants,” Dr. Kallapur says.
Dr. Dargaville reports personal fees from AbbVie and Chiesi Farmaceutici and provision of surfactant at reduced cost and support for conference travel from Chiesi Farmaceutici during the conduct of the study; in addition, Dr. Dargaville has been issued a patent for a catheter design. One coauthor reports grants from Chiesi Farmaceutici during the conduct of the study. Another coauthor reports serving as chief investigator for OPTI-SURF, an observational study on United Kingdom neonatal surfactant use in respiratory distress syndrome funded by Chiesi UK outside the submitted work. A third coauthor reports personal fees from Chiesi Farmaceutici outside the submitted work. This study was funded by grants from the Royal Hobart Hospital Research Foundation and the Australian National Health and Medical Research Council. Exogenous surfactant was provided at reduced cost by Chiesi Farmaceutici. Dr. Kallapur has no relevant financial relationships.
Results of the OPTIMIST follow-up study were published online in JAMA.
Researchers, led by Peter A. Dargaville, MD, department of paediatrics, Royal Hobart (Australia) Hospital, found that MIST, which involves administering surfactant via a thin catheter, compared with sham treatment, did not reduce the incidence of death or neurodevelopmental disability (NDD) by 2 years of age.
However, infants who received MIST had lower rates of poor respiratory outcomes during those first 2 years of life.
Study spanned 11 countries
The study was conducted in 33 tertiary neonatal intensive care units (NICUs) in 11 countries, including Australia, Canada, Israel, New Zealand, Qatar, Singapore, Slovenia, the Netherlands, Turkey, the United Kingdom, and the United States.
It included 486 infants 25-28 weeks old supported with CPAP; 453 had follow-up data available and data on the key secondary outcome were available for 434 infants.
The sham treatment consisted of only transient repositioning without airway instruments. Treating clinicians, outcome assessors, and parents were blinded to group status.
No significant difference in deaths, NDD
Death or NDD occurred in 36.3% of the patients in the MIST group and 36.1% in the control group (risk difference, 0%; 95% confidence interval, −7.6% to 7.7%; relative risk, 1.0; 95% confidence interval, 0.81-1.24).
Secondary respiratory outcomes were better in the MIST group:
- Hospitalization with respiratory illness occurred in 25.1% in the MIST group versus 38.2% in the control group (RR, 0.66; 95% CI, 0.54-0.81).
- Parent-reported wheezing or breathing difficulty occurred in 40.6% in the MIST group versus 53.6% in controls (RR, 0.76; 95% CI, 0.63-0.90).
- Asthma diagnosed by a physician was reported in 4.4% and 11.9% of MIST and control-group infants, respectively.
- Reported use of inhaled relievers (beta2 agonists) was 23.9% in the MIST group versus 38.7% in controls.
The previous study of early outcomes of deaths or bronchopulmonary dysplasia (BPD; chronic lung injury in preterm infants) was published by the same group of researchers in 2021.
Important benefit for respiratory health
Suhas G. Kallapur, MD, chief of the divisions of neonatology and developmental biology at University of California, Los Angeles, who was not part of either study, said: “This is one of the largest studies to date examining whether the MIST procedure for surfactant is beneficial in preterm babies born at 25-28 weeks’ gestation.”
Overall, when considering the 2021 and 2023 studies together, it appears that the MIST therapy has important benefits for respiratory health during a NICU stay and in early infancy, even though the primary outcome of death or NDD was not different between the treatment and control groups, Dr. Kallapur said.
“The slight (nonsignificant) increase in deaths in the MIST group was confined to the more immature babies – 25-26 weeks’ gestation at birth,” he pointed out. “In the bigger and more mature babies – 27-28 week gestation infants – the benefits of MIST therapy occurred without any increase in mortality, suggesting that this group of babies may be the group that stands to benefit most from this therapy.”
Dr. Kallapur said new data in the developmental origins of health and disease “now show that the trajectory of respiratory health in infancy is an important determinant of respiratory health into adulthood and older age.”
Therefore, the finding of benefit to respiratory health is particularly important, he said.
He noted that MIST or similar therapy is already in use in many NICUs throughout the world and that those already using it will likely feel vindicated by this study.
“Neonatologists who were on the sidelines will likely see these results – especially childhood respiratory outcomes – as a reason to initiate this procedure in all but the most immature preterm infants,” Dr. Kallapur says.
Dr. Dargaville reports personal fees from AbbVie and Chiesi Farmaceutici and provision of surfactant at reduced cost and support for conference travel from Chiesi Farmaceutici during the conduct of the study; in addition, Dr. Dargaville has been issued a patent for a catheter design. One coauthor reports grants from Chiesi Farmaceutici during the conduct of the study. Another coauthor reports serving as chief investigator for OPTI-SURF, an observational study on United Kingdom neonatal surfactant use in respiratory distress syndrome funded by Chiesi UK outside the submitted work. A third coauthor reports personal fees from Chiesi Farmaceutici outside the submitted work. This study was funded by grants from the Royal Hobart Hospital Research Foundation and the Australian National Health and Medical Research Council. Exogenous surfactant was provided at reduced cost by Chiesi Farmaceutici. Dr. Kallapur has no relevant financial relationships.
FROM JAMA
FDA panel deems phenylephrine ineffective
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.
The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.
A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.
“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.
The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.
The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.
Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.
Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.
Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.
According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.
“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.
She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.
“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.
According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”
Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”
These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.
A version of this article appeared on Medscape.com.
Navigating chronic cough in primary care
Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”
“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.
“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
Understanding the multifaceted nature of chronic cough
Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.
Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.
Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
Effective management strategies
Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.
The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.
“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.
Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
Current treatments and future prospects
Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.
Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.
Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.
“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.
Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.
A version of this article first appeared on Medscape.com.
Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”
“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.
“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
Understanding the multifaceted nature of chronic cough
Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.
Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.
Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
Effective management strategies
Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.
The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.
“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.
Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
Current treatments and future prospects
Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.
Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.
Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.
“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.
Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.
A version of this article first appeared on Medscape.com.
Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”
“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.
“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
Understanding the multifaceted nature of chronic cough
Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.
Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.
Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
Effective management strategies
Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.
The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.
“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.
Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
Current treatments and future prospects
Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.
Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.
Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.
“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.
Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.
A version of this article first appeared on Medscape.com.
FROM ERS 2023
Growing public perception that cannabis is safer than tobacco
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.
Adaptive treatment aids smoking cessation
Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.
Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.
Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.
A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.
The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.
After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.
At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).
In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).
No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.
The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.
However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.
The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.
Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.
Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.
Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.
A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.
The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.
After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.
At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).
In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).
No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.
The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.
However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.
The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.
Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.
Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.
In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.
Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.
A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.
The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.
After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.
At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).
In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).
No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.
The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.
However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.
The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
When does a bicarb drip make sense?
A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.
Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
What do the data reveal?
An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.
The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.
The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO2 of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.
That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.
Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.
Our patient had AKI, a pH of 7.20 or less, and a pCO2 well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
Key takeaways
Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.
Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
What do the data reveal?
An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.
The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.
The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO2 of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.
That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.
Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.
Our patient had AKI, a pH of 7.20 or less, and a pCO2 well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
Key takeaways
Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.
Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
What do the data reveal?
An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.
The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.
The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO2 of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.
That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.
Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.
Our patient had AKI, a pH of 7.20 or less, and a pCO2 well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
Key takeaways
Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Young vapers and smokers beware: Eye problems abound
Adolescents and young adults who smoked and vaped were more likely to report ocular problems including dryness, redness, pain, blurry vision, light sensitivity, and headaches, according to an observational study published in JAMA Ophthalmology.
Eye symptoms were significantly worse among young people who reported using both cigarettes and e-cigarettes than for those who said they used only one of the products, according to researchers. Symptoms were particularly frequent and severe among those who had used both products in the prior week.
“In ophthalmology clinics, I’ve increasingly noticed patients, particularly adolescents and young adults, presenting with eye-related symptoms such as dryness, irritation, and even vision disturbances,” said Anne Xuan-Lan Nguyen, MDCM, an ophthalmology resident at the University of Toronto, who led the study.
Many of these patients said they did not use contact lenses or take medications associated with eye problems, but they did report a history of using e-cigarettes and cigarettes.
This “sparked my curiosity about the possible link between smoking or vaping and ocular symptoms,” Dr. Nguyen, who conducted the research as a medical student at McGill University in Montreal, told this news organization.
E-cigarettes are the most popular tobacco product among young people. Public health data show an increasing trend toward both vaping and smoking cigarettes, known as dual use. An estimated 40% of middle- and high school–aged tobacco users report using two or more tobacco products, according to the Centers for Disease Control and Prevention. Cigarette use has been linked to ocular damage, but the effects of e-cigarettes on eyesight and the combined effect with cigarettes are not as well known.
Dr. Nguyen and her colleagues surveyed more than 4,000 people aged 13-24 about their use of cigarettes or e-cigarettes in the last 30 days, the last 7 days, or ever. Half said they had never used any tobacco product and one quarter reported having used cigarettes, vapes, or both in the last month. More than 900 respondents said they had used one or both tobacco products in the last week.
Of the respondents who had ever vaped, 55.9% said they also used cigarettes. These dual users reported more severe and frequent eye symptoms compared with users of either product alone. Up to 4% of respondents who had ever been a dual user reported daily, severe, or very severe ocular symptoms – more than in the cigarette-only or e-cigarette-only groups.
More frequent tobacco use also was associated with more ocular symptoms. Young people who smoked or vaped in the previous week reported more symptoms than did the 30-day group, who reported more symptoms than the ever-user group (those who had taken at least a puff but not in the last month).
“All these conditions we know are worse as you get older,” said Laura B. Enyedi, MD, pediatric ophthalmologist at the Duke Eye Center in Durham, N.C., who was not associated with the study. “So if young people are having symptoms, it doesn’t bode well for them as they age.”
E-cigarette use alone did not appear to be linked to eye ailments, according to the findings. But to Dr. Nguyen’s surprise the survey results showed users of vaping products spent the most time worried about their eye health compared with all other participants. Users who smoked only cigarettes reported ocular symptoms, but not as severe or frequent as those of dual users.
The researchers hypothesized that ocular problems caused by vapes and cigarettes could be classified as oxidative damage. The combustion of the cigarette and the e-cigarette solvent (propylene glycol) potentially generates free radicals that can cause oxidative stress, damaging the ocular surface and film, Dr. Nguyen said.
Ophthalmologists are “always asking about contact lens use, lid hygiene, and screen time. Here’s another thing to consider when we get those common, nonspecific complaints of symptoms like dryness, redness, and burning,” Dr. Enyedi said.
Given the observational nature of the study, the researchers cannot confirm that dual use causes ocular symptoms. But given the public health challenge that tobacco use already presents for young people, the findings provide yet another reason to counsel against tobacco use and provide cessation options, Dr. Nguyen said.
“This study is just one of many, many studies showing a significant relationship among smoking, e-cigarette use, and health outcomes,” said Bonnie Halpern-Felsher, PhD, professor of pediatrics at Stanford (Calif.) University and a coauthor of the study. “We clearly need to help young people not use at all, or quit or cut back if using.”
This study was supported by the Taube Research Faculty Scholar Endowment; the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; the National Cancer Institute; the Stanford Maternal and Child Health Research Institute; and the Research to Prevent Blindness and National Eye Institute. Dr. Halpern-Felsher reported receiving personal fees as an expert scientist in litigation against some e-cigarette companies. The other study authors and Dr. Enyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adolescents and young adults who smoked and vaped were more likely to report ocular problems including dryness, redness, pain, blurry vision, light sensitivity, and headaches, according to an observational study published in JAMA Ophthalmology.
Eye symptoms were significantly worse among young people who reported using both cigarettes and e-cigarettes than for those who said they used only one of the products, according to researchers. Symptoms were particularly frequent and severe among those who had used both products in the prior week.
“In ophthalmology clinics, I’ve increasingly noticed patients, particularly adolescents and young adults, presenting with eye-related symptoms such as dryness, irritation, and even vision disturbances,” said Anne Xuan-Lan Nguyen, MDCM, an ophthalmology resident at the University of Toronto, who led the study.
Many of these patients said they did not use contact lenses or take medications associated with eye problems, but they did report a history of using e-cigarettes and cigarettes.
This “sparked my curiosity about the possible link between smoking or vaping and ocular symptoms,” Dr. Nguyen, who conducted the research as a medical student at McGill University in Montreal, told this news organization.
E-cigarettes are the most popular tobacco product among young people. Public health data show an increasing trend toward both vaping and smoking cigarettes, known as dual use. An estimated 40% of middle- and high school–aged tobacco users report using two or more tobacco products, according to the Centers for Disease Control and Prevention. Cigarette use has been linked to ocular damage, but the effects of e-cigarettes on eyesight and the combined effect with cigarettes are not as well known.
Dr. Nguyen and her colleagues surveyed more than 4,000 people aged 13-24 about their use of cigarettes or e-cigarettes in the last 30 days, the last 7 days, or ever. Half said they had never used any tobacco product and one quarter reported having used cigarettes, vapes, or both in the last month. More than 900 respondents said they had used one or both tobacco products in the last week.
Of the respondents who had ever vaped, 55.9% said they also used cigarettes. These dual users reported more severe and frequent eye symptoms compared with users of either product alone. Up to 4% of respondents who had ever been a dual user reported daily, severe, or very severe ocular symptoms – more than in the cigarette-only or e-cigarette-only groups.
More frequent tobacco use also was associated with more ocular symptoms. Young people who smoked or vaped in the previous week reported more symptoms than did the 30-day group, who reported more symptoms than the ever-user group (those who had taken at least a puff but not in the last month).
“All these conditions we know are worse as you get older,” said Laura B. Enyedi, MD, pediatric ophthalmologist at the Duke Eye Center in Durham, N.C., who was not associated with the study. “So if young people are having symptoms, it doesn’t bode well for them as they age.”
E-cigarette use alone did not appear to be linked to eye ailments, according to the findings. But to Dr. Nguyen’s surprise the survey results showed users of vaping products spent the most time worried about their eye health compared with all other participants. Users who smoked only cigarettes reported ocular symptoms, but not as severe or frequent as those of dual users.
The researchers hypothesized that ocular problems caused by vapes and cigarettes could be classified as oxidative damage. The combustion of the cigarette and the e-cigarette solvent (propylene glycol) potentially generates free radicals that can cause oxidative stress, damaging the ocular surface and film, Dr. Nguyen said.
Ophthalmologists are “always asking about contact lens use, lid hygiene, and screen time. Here’s another thing to consider when we get those common, nonspecific complaints of symptoms like dryness, redness, and burning,” Dr. Enyedi said.
Given the observational nature of the study, the researchers cannot confirm that dual use causes ocular symptoms. But given the public health challenge that tobacco use already presents for young people, the findings provide yet another reason to counsel against tobacco use and provide cessation options, Dr. Nguyen said.
“This study is just one of many, many studies showing a significant relationship among smoking, e-cigarette use, and health outcomes,” said Bonnie Halpern-Felsher, PhD, professor of pediatrics at Stanford (Calif.) University and a coauthor of the study. “We clearly need to help young people not use at all, or quit or cut back if using.”
This study was supported by the Taube Research Faculty Scholar Endowment; the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; the National Cancer Institute; the Stanford Maternal and Child Health Research Institute; and the Research to Prevent Blindness and National Eye Institute. Dr. Halpern-Felsher reported receiving personal fees as an expert scientist in litigation against some e-cigarette companies. The other study authors and Dr. Enyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adolescents and young adults who smoked and vaped were more likely to report ocular problems including dryness, redness, pain, blurry vision, light sensitivity, and headaches, according to an observational study published in JAMA Ophthalmology.
Eye symptoms were significantly worse among young people who reported using both cigarettes and e-cigarettes than for those who said they used only one of the products, according to researchers. Symptoms were particularly frequent and severe among those who had used both products in the prior week.
“In ophthalmology clinics, I’ve increasingly noticed patients, particularly adolescents and young adults, presenting with eye-related symptoms such as dryness, irritation, and even vision disturbances,” said Anne Xuan-Lan Nguyen, MDCM, an ophthalmology resident at the University of Toronto, who led the study.
Many of these patients said they did not use contact lenses or take medications associated with eye problems, but they did report a history of using e-cigarettes and cigarettes.
This “sparked my curiosity about the possible link between smoking or vaping and ocular symptoms,” Dr. Nguyen, who conducted the research as a medical student at McGill University in Montreal, told this news organization.
E-cigarettes are the most popular tobacco product among young people. Public health data show an increasing trend toward both vaping and smoking cigarettes, known as dual use. An estimated 40% of middle- and high school–aged tobacco users report using two or more tobacco products, according to the Centers for Disease Control and Prevention. Cigarette use has been linked to ocular damage, but the effects of e-cigarettes on eyesight and the combined effect with cigarettes are not as well known.
Dr. Nguyen and her colleagues surveyed more than 4,000 people aged 13-24 about their use of cigarettes or e-cigarettes in the last 30 days, the last 7 days, or ever. Half said they had never used any tobacco product and one quarter reported having used cigarettes, vapes, or both in the last month. More than 900 respondents said they had used one or both tobacco products in the last week.
Of the respondents who had ever vaped, 55.9% said they also used cigarettes. These dual users reported more severe and frequent eye symptoms compared with users of either product alone. Up to 4% of respondents who had ever been a dual user reported daily, severe, or very severe ocular symptoms – more than in the cigarette-only or e-cigarette-only groups.
More frequent tobacco use also was associated with more ocular symptoms. Young people who smoked or vaped in the previous week reported more symptoms than did the 30-day group, who reported more symptoms than the ever-user group (those who had taken at least a puff but not in the last month).
“All these conditions we know are worse as you get older,” said Laura B. Enyedi, MD, pediatric ophthalmologist at the Duke Eye Center in Durham, N.C., who was not associated with the study. “So if young people are having symptoms, it doesn’t bode well for them as they age.”
E-cigarette use alone did not appear to be linked to eye ailments, according to the findings. But to Dr. Nguyen’s surprise the survey results showed users of vaping products spent the most time worried about their eye health compared with all other participants. Users who smoked only cigarettes reported ocular symptoms, but not as severe or frequent as those of dual users.
The researchers hypothesized that ocular problems caused by vapes and cigarettes could be classified as oxidative damage. The combustion of the cigarette and the e-cigarette solvent (propylene glycol) potentially generates free radicals that can cause oxidative stress, damaging the ocular surface and film, Dr. Nguyen said.
Ophthalmologists are “always asking about contact lens use, lid hygiene, and screen time. Here’s another thing to consider when we get those common, nonspecific complaints of symptoms like dryness, redness, and burning,” Dr. Enyedi said.
Given the observational nature of the study, the researchers cannot confirm that dual use causes ocular symptoms. But given the public health challenge that tobacco use already presents for young people, the findings provide yet another reason to counsel against tobacco use and provide cessation options, Dr. Nguyen said.
“This study is just one of many, many studies showing a significant relationship among smoking, e-cigarette use, and health outcomes,” said Bonnie Halpern-Felsher, PhD, professor of pediatrics at Stanford (Calif.) University and a coauthor of the study. “We clearly need to help young people not use at all, or quit or cut back if using.”
This study was supported by the Taube Research Faculty Scholar Endowment; the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; the National Cancer Institute; the Stanford Maternal and Child Health Research Institute; and the Research to Prevent Blindness and National Eye Institute. Dr. Halpern-Felsher reported receiving personal fees as an expert scientist in litigation against some e-cigarette companies. The other study authors and Dr. Enyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA OPHTHALMOLOGY
Mepolizumab improves asthma after 1 year despite comorbidities
Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.
Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.
“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.
In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.
To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.
The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).
Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.
“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.
The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).
In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV1) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.
Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV1 improvement in patients with vs. without COPD.
“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.
The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.
“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.
The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.
Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.
Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.
“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.
In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.
To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.
The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).
Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.
“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.
The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).
In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV1) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.
Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV1 improvement in patients with vs. without COPD.
“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.
The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.
“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.
The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.
Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.
Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.
“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.
In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.
To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.
The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).
Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.
“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.
The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).
In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV1) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.
Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV1 improvement in patients with vs. without COPD.
“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.
The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.
“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.
The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.
FROM THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY: IN PRACTICE
Screening finds high rates of CVD in diabetes, COPD patients
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AT ESC CONGRESS 2023