User login
What are the signs of post–acute infection syndromes?
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.
PAIS, PASC, or long COVID
The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.
Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.
PAIS are characterized by a set of core symptoms centering on the following:
- Exertion intolerance
- Disproportionate levels of fatigue
- Neurocognitive and sensory impairment
- Flu-like symptoms
- Unrefreshing sleep
- Myalgia/arthralgia
A plethora of nonspecific symptoms are often present to various degrees.
These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
Overview of PAIS
A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.
The following consolidated postinfection sequelae are mentioned:
- Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
- Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
- Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
- Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
- Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
- Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.
Symptoms and signs
The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:
- Exertion intolerance, fatigue
- Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
- Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
- Rheumatologic symptoms: chronic or recurrent joint pain
- Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus
Myalgic encephalomyelitis/chronic fatigue syndrome
Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.
Practical diagnostic criteria
From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.
Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.
This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.
IL-6 antibody mitigates mucus hypersecretion in COPD
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.
AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.
Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.
In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.
The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.
The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.
IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).
The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.
The study findings were limited by the relatively small study population from a single center, the researchers noted.
However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.
The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.
FROM BIOMEDICINE & PHARMACOTHERAPY
Eosinophils may predict outcomes in acute COPD exacerbations
High levels of eosinophils had a protective effect for individuals who experienced acute exacerbations of chronic obstructive pulmonary disease, based on data from nearly 1,000 patients.
Several blood biomarkers are under investigation for links to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), which remains one of the top three causes of death worldwide, wrote Riuying Wang, MD, of Third Hospital of Shanxi Medical University, Taiyuan, China, and colleagues.
“Numerous studies have shown the relationship between eosinophilia and clinical outcomes of patients with AECOPD. However, the evidence lacks consensus, and the research thresholds are controversial,” they said.
In a study published in Heart & Lung, the researchers reviewed data from 984 adults with AECOPD over a 3-year follow-up period. The mean age of the patients was 71 years, and 78% were men. The patients’ blood eosinophil levels were grouped into three categories: EOS < 2%, EOS from 2% to < 3%, and 3% or higher. The researchers examined the association between eosinophilia and various comorbidities, treatment, and mortality.
Eosinophilia occurred in 477 cases. The prevalence of eosinophilia in the three groups was 36.48%, 22.87%, and 48.48% respectively, with eosinophilia defined as eosinophil counts of at least 100 cells per microliter, according to the report in Heart & Lung.
An EOS of 2% or higher was associated with significantly fewer cases of complicated pulmonary heart disease and atrial fibrillation than the lower EOS group. Similarly, patients in the EOS group of 2% or higher were less likely to use ventilators and systemic glucocorticoids and those in the EOS less than 2% group had significantly heavier airflow limitation, higher D-dimer, higher burden of infectious inflammation, and higher prevalence of respiratory failure than the other groups.
In addition, significantly fewer deaths occurred during the study period among patients with EOS of 2% or higher, compared with the lower EOS group (P < .01). The findings suggest that “Eosinophils can be used as a prognostic indicator of mortality in AECOPD,” the researchers said.
The researchers also used the area under the curve to examine the predictive value of EOS. The ROC curve showed that the indicators of AUC 0.5 included chest CT imaging, osteoporosis, mental illness, dust exposure, and being a former smoker; however, “the predictive value of EOS by the ROC curve was unstable. Further validation in large samples is needed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the relatively small sample size and a lack of data on some clinical features and performance metrics, as well as lack of evaluation of chest CT subtypes.
However, the results are consistent with previous studies on infection and antibiotics and reviewed the optimal threshold of AECOPD, the researchers wrote. Based on their findings, “Eosinophils can not only guide clinical treatment but also be used as an index to predict the clinical outcome and prognosis of AECOPD patients,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
High levels of eosinophils had a protective effect for individuals who experienced acute exacerbations of chronic obstructive pulmonary disease, based on data from nearly 1,000 patients.
Several blood biomarkers are under investigation for links to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), which remains one of the top three causes of death worldwide, wrote Riuying Wang, MD, of Third Hospital of Shanxi Medical University, Taiyuan, China, and colleagues.
“Numerous studies have shown the relationship between eosinophilia and clinical outcomes of patients with AECOPD. However, the evidence lacks consensus, and the research thresholds are controversial,” they said.
In a study published in Heart & Lung, the researchers reviewed data from 984 adults with AECOPD over a 3-year follow-up period. The mean age of the patients was 71 years, and 78% were men. The patients’ blood eosinophil levels were grouped into three categories: EOS < 2%, EOS from 2% to < 3%, and 3% or higher. The researchers examined the association between eosinophilia and various comorbidities, treatment, and mortality.
Eosinophilia occurred in 477 cases. The prevalence of eosinophilia in the three groups was 36.48%, 22.87%, and 48.48% respectively, with eosinophilia defined as eosinophil counts of at least 100 cells per microliter, according to the report in Heart & Lung.
An EOS of 2% or higher was associated with significantly fewer cases of complicated pulmonary heart disease and atrial fibrillation than the lower EOS group. Similarly, patients in the EOS group of 2% or higher were less likely to use ventilators and systemic glucocorticoids and those in the EOS less than 2% group had significantly heavier airflow limitation, higher D-dimer, higher burden of infectious inflammation, and higher prevalence of respiratory failure than the other groups.
In addition, significantly fewer deaths occurred during the study period among patients with EOS of 2% or higher, compared with the lower EOS group (P < .01). The findings suggest that “Eosinophils can be used as a prognostic indicator of mortality in AECOPD,” the researchers said.
The researchers also used the area under the curve to examine the predictive value of EOS. The ROC curve showed that the indicators of AUC 0.5 included chest CT imaging, osteoporosis, mental illness, dust exposure, and being a former smoker; however, “the predictive value of EOS by the ROC curve was unstable. Further validation in large samples is needed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the relatively small sample size and a lack of data on some clinical features and performance metrics, as well as lack of evaluation of chest CT subtypes.
However, the results are consistent with previous studies on infection and antibiotics and reviewed the optimal threshold of AECOPD, the researchers wrote. Based on their findings, “Eosinophils can not only guide clinical treatment but also be used as an index to predict the clinical outcome and prognosis of AECOPD patients,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
High levels of eosinophils had a protective effect for individuals who experienced acute exacerbations of chronic obstructive pulmonary disease, based on data from nearly 1,000 patients.
Several blood biomarkers are under investigation for links to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), which remains one of the top three causes of death worldwide, wrote Riuying Wang, MD, of Third Hospital of Shanxi Medical University, Taiyuan, China, and colleagues.
“Numerous studies have shown the relationship between eosinophilia and clinical outcomes of patients with AECOPD. However, the evidence lacks consensus, and the research thresholds are controversial,” they said.
In a study published in Heart & Lung, the researchers reviewed data from 984 adults with AECOPD over a 3-year follow-up period. The mean age of the patients was 71 years, and 78% were men. The patients’ blood eosinophil levels were grouped into three categories: EOS < 2%, EOS from 2% to < 3%, and 3% or higher. The researchers examined the association between eosinophilia and various comorbidities, treatment, and mortality.
Eosinophilia occurred in 477 cases. The prevalence of eosinophilia in the three groups was 36.48%, 22.87%, and 48.48% respectively, with eosinophilia defined as eosinophil counts of at least 100 cells per microliter, according to the report in Heart & Lung.
An EOS of 2% or higher was associated with significantly fewer cases of complicated pulmonary heart disease and atrial fibrillation than the lower EOS group. Similarly, patients in the EOS group of 2% or higher were less likely to use ventilators and systemic glucocorticoids and those in the EOS less than 2% group had significantly heavier airflow limitation, higher D-dimer, higher burden of infectious inflammation, and higher prevalence of respiratory failure than the other groups.
In addition, significantly fewer deaths occurred during the study period among patients with EOS of 2% or higher, compared with the lower EOS group (P < .01). The findings suggest that “Eosinophils can be used as a prognostic indicator of mortality in AECOPD,” the researchers said.
The researchers also used the area under the curve to examine the predictive value of EOS. The ROC curve showed that the indicators of AUC 0.5 included chest CT imaging, osteoporosis, mental illness, dust exposure, and being a former smoker; however, “the predictive value of EOS by the ROC curve was unstable. Further validation in large samples is needed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the relatively small sample size and a lack of data on some clinical features and performance metrics, as well as lack of evaluation of chest CT subtypes.
However, the results are consistent with previous studies on infection and antibiotics and reviewed the optimal threshold of AECOPD, the researchers wrote. Based on their findings, “Eosinophils can not only guide clinical treatment but also be used as an index to predict the clinical outcome and prognosis of AECOPD patients,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM HEART & LUNG
Sleep, not smoke, the key to COPD exacerbations?
, according to a study reported online in the journal Sleep.
Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.
COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.
Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.
There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).
In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
Surprising findings
These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.
“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.
The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.
The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.
, according to a study reported online in the journal Sleep.
Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.
COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.
Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.
There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).
In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
Surprising findings
These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.
“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.
The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.
The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.
, according to a study reported online in the journal Sleep.
Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.
COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.
Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.
There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).
In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
Surprising findings
These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.
“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.
The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.
The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.
FROM SLEEP
2022 GOLD Report: Tips for diagnosing and evaluating COPD
For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.
The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.
The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
2022 GOLD Report
For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.
The report suggests that COPD is being underdiagnosed.
Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.
For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.
The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.
Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.
The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.
To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV1/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).
Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.
Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.
Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.
The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.
The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
2022 GOLD Report
For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.
The report suggests that COPD is being underdiagnosed.
Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.
For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.
The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.
Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.
The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.
To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV1/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).
Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.
Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.
Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.
The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.
The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
2022 GOLD Report
For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.
The report suggests that COPD is being underdiagnosed.
Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.
For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.
The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.
Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.
The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.
To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV1/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).
Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.
Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.
Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
Updates on eosinophilia in asthma
Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.
In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).
However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).
More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV1). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).
What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.
But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?
A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).
Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).
Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.
So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.
Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.
Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.
Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.
In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).
However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).
More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV1). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).
What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.
But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?
A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).
Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).
Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.
So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.
Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.
Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.
Our understanding of asthma endotypes and phenotypes has grown substantially in the last decade. Endotype-targeted therapy has become a foundation of management, and classification of patients during initial assessment is extremely important. The use of history, laboratory data, and pulmonary function testing together help to categorize our patients and help guide therapy. One lab test, that of sputum or blood eosinophils, facilitates categorization and has been evaluated for its ability to determine response to medications and predict exacerbations.
In particular, eosinophilia has been extensively studied in severe asthma and is associated with type 2 inflammation. The 2021 GINA guidelines describe type 2 inflammation as characterized by cytokines (especially IL-4, IL-5, and IL-13). “T2-high patients” tend to have elevated blood or sputum eosinophil counts and elevated fractional concentration of exhaled nitric oxide (FENO) and are more likely to respond to biologic therapy. (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021).
However, what about patients with more mild-to-moderate asthma? Two recent studies have asked this question. In 2020, Pavord and colleagues performed a prespecified secondary subgroup analysis on an open-label randomized control trial comparing prn salbutamol alone to budesonide and as needed salbutamol to as needed budesonide-formoterol. The population was 675 adults with mild asthma receiving only as needed short acting beta-agonists (SABA) at baseline. The primary outcome was annual rate of asthma exacerbation, and whether it was different based on blood eosinophil count, FENO or a composite of both. They had several interesting findings. First, for patients only on an as needed SABA, the proportion having a severe exacerbation increased progressively with increasing blood eosinophil count. Second, inhaled corticosteroids (ICS) plus as needed SABA were more effective than SABA alone in patients with a blood eosinophil count of ≥300 cells/μL, both in terms of total exacerbations and severe exacerbations. The effects of budesonide-formoterol on exacerbations, however, was not associated with blood eosinophil count or FENO. This last point is particularly interesting in light of GINA guidelines that prioritize this combination (Pavord ID et al. Lancet Respir Med. 2020;8[7]:671-80).
More recently, a prespecified secondary analysis of the SIENA trial looked at 295 subjects with mild persistent asthma (237 adults aged 18+, and 58 adolescents aged 12-17). The primary outcome was a composite of asthma control (treatment failure, asthma control days, and FEV1). They found that sputum eosinophil levels, blood eosinophil levels, and FENO all predicted response to ICS in adults; however, the area under the receiver operative characteristic curve (AUC) was less than 0.7 for each of these findings, which was below the threshold for acceptability. A blood eosinophil count of ≥100 cells/μL offered 87% sensitivity and 17% specificity for response to ICS (Krishnan JA et al. Ann Am Thorac Soc. 2022;19[3]:372-80).
What does this tell us? Blood eosinophil count may help determine who will respond to ICS, and there remains utility in assessing blood eosinophil count in severe asthma for determining candidacy for biologic therapies. However, the overall utility of blood eosinophils in mild to moderate asthma is not as clear.
But, are we asking the right questions? Many studies look at a single blood eosinophil level, either at a single point in time, a baseline level, or a highest level over a specific time period. But do eosinophil counts vary over time?
A 2018 single-center study initially asked this question. The authors evaluated blood eosinophil levels in 219 adult patients at the NYU/Bellevue Hospital Asthma Clinic over a 5-year period. They found that individual patients had variable eosinophil levels. For example, only 6% (n=13) of patients had levels consistently above 300 cells/μL, but nearly 50% (n=104) had at least one level above 300. The degree of variability was then assessed by K-mean clustering yielding three clusters. Cluster 2 had the largest variability in blood eosinophil counts and a slightly higher absolute eosinophil level. While not significant, there was a suggestion of worse asthma control with more hospitalizations and more prescriptions for multiple controllers in this cluster with more variability. Clearly, this warranted further study (Rakowski E et al. Clin Exp Allergy. 2019;49[2]:163-70).
Variability was re-examined more recently in 2021. A post hoc analysis of two phase III clinical trials from the reslizumab BREATH program looked at eosinophil counts in the 476 patients randomized to receive placebo during the 52-week study. These patients did have eosinophilic asthma by definition and had to have an elevated eosinophil count >400 cells/μL over the 4-week enrollment period to enter the study. However, 124 patients (26.1%) had an eosinophil level <400 cells/μL immediately before the first dose of placebo. The primary outcome was variability in blood eosinophil count. Of patients who started with serum eosinophils <400, 27% to 56% of patients shifted to the ≥400 cells/μL category during the treatment period (this wide range is across three categories of low “baseline” blood eosinophil count; <150, 150 to 300, and 300 to 400). On the contrary, patients who started with eosinophils ≥400 cells/μL tended to stay at that level. The variability is reduced by taking two to three repeat measurements at baseline (Corren et al. J Allergy Clin Immunol Pract. 2021;9[3]:1224-31).
Does this variability have clinical significance? A recent retrospective cohort study looked at 10,059 stable adult patients with asthma from the MAJORICA cohort in Spain, compared with 8,557 control subjects. The primary outcome was total blood eosinophil count and an “eosinophil variability index” (EVI) where EVI=(Eosmax – Eosmin / Eosmax) x 100%. They found that an elevated EVI was associated with hospitalization, more so than maximum eosinophil count or any other eosinophil count variable, with an odds ratio of 3.18 by univariate regression (2.51 by multivariate). They also found that patients with an EVI ≥50% were twice as likely to be hospitalized or visit the ED than those with a lower EVI (Toledo-Pons N et al. Ann Am Thorac Soc. 2022;19[3]:407-14). These results are very interesting and merit further research.
So, what to do with this information? We know that patients with peripheral eosinophilia and severe asthma symptoms are candidates for biologic therapy. They are also more likely to respond to steroids, although the utility of this assessment alone in mild to moderate asthma is less clear. It does seem that more variability in eosinophils over time may be linked to more difficult-to-treat asthma.
Should you check eosinophils in your patients with asthma? GINA 2021 guidelines say to consider it, and list blood eosinophilia as a risk factor for future exacerbation, even if patients have few asthma symptoms. They also say to repeat blood eosinophils in patients with severe asthma, if the level is low at first assessment, based on the studies discussed above. We would agree. We also see the blood eosinophil count as one part of a clinical assessment of a patient’s overall asthma control – even if the patient has mild symptoms. More study on variability is welcome.
Dr. Haber and Dr. Jamieson are with Medstar Georgetown University Hospital, Washington, D.C.
Harmony pulmonary valve update: Regurgitation resolved 1 year out
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
FROM SCAI 2022
FDA warning released for Volara respiratory system
The Food and Drug Administration published a warning from the medical device company Baxter International, citing problems with their device used for at-home respiratory therapy. The release cautions Volara system users that using certain therapies from the device may cause a change in lung pressure and a decrease in oxygen level. This cautionary warning was issued following a single reported case of oxygen loss while using the device.
The Volara system is meant to help patients with persistent pulmonary problems who are transitioning from the hospital to the outpatient setting. It can connect to three pieces commonly used in treating the respiratory conditions – a tracheostomy tube, a mask, and an in-line ventilator. The device offers three therapies – one to expand lungs (OLE), one to shake mucus from the lungs (CHFO), and a nebulizer to deliver medication.
This particular warning is relevant only to patients who use the system with an in-line ventilator or to patients who use OLE and CHFO therapies. The concern is that a rapid change in lung pressure (barotrauma), could damage the tissue by overextending the surface of the organ. Additionally, as noted in the reported case, Volara users may be at risk for a decrease in the level of oxygen while using the device (oxygen desaturation).
If patients have been directed to use Volara by a physician, the FDA recommends they continue to use it as prescribed. But they should look out for signs of respiratory distress. These include changes in alertness, the appearance of a blue tint around the mouth, increased breathing rate, and wheezing. If a patient or caregiver sees these signs, the patient should stop using Volara immediately and should seek help if their symptoms don’t improve.
In response to these precautions, Baxter says it will update the instructions for the use of its device and will add additional warnings. The company says it will dispatch a trainer to patients’ homes to help them understand the newest guidelines.
Both the FDA and Baxter urge patients who have experienced any problems with the device to report it to the hotlines listed at the bottom of their release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration published a warning from the medical device company Baxter International, citing problems with their device used for at-home respiratory therapy. The release cautions Volara system users that using certain therapies from the device may cause a change in lung pressure and a decrease in oxygen level. This cautionary warning was issued following a single reported case of oxygen loss while using the device.
The Volara system is meant to help patients with persistent pulmonary problems who are transitioning from the hospital to the outpatient setting. It can connect to three pieces commonly used in treating the respiratory conditions – a tracheostomy tube, a mask, and an in-line ventilator. The device offers three therapies – one to expand lungs (OLE), one to shake mucus from the lungs (CHFO), and a nebulizer to deliver medication.
This particular warning is relevant only to patients who use the system with an in-line ventilator or to patients who use OLE and CHFO therapies. The concern is that a rapid change in lung pressure (barotrauma), could damage the tissue by overextending the surface of the organ. Additionally, as noted in the reported case, Volara users may be at risk for a decrease in the level of oxygen while using the device (oxygen desaturation).
If patients have been directed to use Volara by a physician, the FDA recommends they continue to use it as prescribed. But they should look out for signs of respiratory distress. These include changes in alertness, the appearance of a blue tint around the mouth, increased breathing rate, and wheezing. If a patient or caregiver sees these signs, the patient should stop using Volara immediately and should seek help if their symptoms don’t improve.
In response to these precautions, Baxter says it will update the instructions for the use of its device and will add additional warnings. The company says it will dispatch a trainer to patients’ homes to help them understand the newest guidelines.
Both the FDA and Baxter urge patients who have experienced any problems with the device to report it to the hotlines listed at the bottom of their release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration published a warning from the medical device company Baxter International, citing problems with their device used for at-home respiratory therapy. The release cautions Volara system users that using certain therapies from the device may cause a change in lung pressure and a decrease in oxygen level. This cautionary warning was issued following a single reported case of oxygen loss while using the device.
The Volara system is meant to help patients with persistent pulmonary problems who are transitioning from the hospital to the outpatient setting. It can connect to three pieces commonly used in treating the respiratory conditions – a tracheostomy tube, a mask, and an in-line ventilator. The device offers three therapies – one to expand lungs (OLE), one to shake mucus from the lungs (CHFO), and a nebulizer to deliver medication.
This particular warning is relevant only to patients who use the system with an in-line ventilator or to patients who use OLE and CHFO therapies. The concern is that a rapid change in lung pressure (barotrauma), could damage the tissue by overextending the surface of the organ. Additionally, as noted in the reported case, Volara users may be at risk for a decrease in the level of oxygen while using the device (oxygen desaturation).
If patients have been directed to use Volara by a physician, the FDA recommends they continue to use it as prescribed. But they should look out for signs of respiratory distress. These include changes in alertness, the appearance of a blue tint around the mouth, increased breathing rate, and wheezing. If a patient or caregiver sees these signs, the patient should stop using Volara immediately and should seek help if their symptoms don’t improve.
In response to these precautions, Baxter says it will update the instructions for the use of its device and will add additional warnings. The company says it will dispatch a trainer to patients’ homes to help them understand the newest guidelines.
Both the FDA and Baxter urge patients who have experienced any problems with the device to report it to the hotlines listed at the bottom of their release.
A version of this article first appeared on Medscape.com.
FDA: Urgent device correction, recall for Philips ventilator
The U.S. Food and Drug Administration has announced a Class I recall for Philips Respironics V60 and V60 Plus ventilators, citing a power failure leading to potential oxygen deprivation. Class I recalls, the most severe, are reserved for devices that may cause serious injury or death, as noted in the FDA’s announcement. As of April 14, one death and four injuries have been associated with this device failure.
These ventilators are commonly used in hospitals or under medical supervision for patients who have difficulty regulating breathing on their own. Normally, if oxygen flow is interrupted, the device sounds alarms, alerting supervisors. The failure comes when a power fluctuation causes the device to randomly shut down, which forces the alarm system to reboot. This internal disruption is the reason for the recall.
When the device shuts down out of the blue, it may or may not sound the requisite alarm that would allow providers to intervene. If the device does not sound the alarm, patients may lose oxygen for an extended period, without a provider even knowing.
Philips was notified of these problems and began the recall process on March 10. Currently, it is estimated that 56,671 devices have been distributed throughout the United States. The FDA and Philips Respironics advise that if providers are already using these ventilators, they may continue to do so in accordance with extra set of instructions.
First, customers should connect the device to an external alarm or nurse call system. Second, they should use an external oxygen monitor and a pulse oximeter to keep track of air flow. Finally, if one is available, there should be a backup ventilator on the premises. That way, if there is an interruption in oxygen flow, someone will be alerted and can quickly intervene.
If there is a problem, the patient should be removed from the Philips ventilator and immediately placed on an alternate device. The FDA instructs customers who have experienced problems to report them to its MedWatch database.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has announced a Class I recall for Philips Respironics V60 and V60 Plus ventilators, citing a power failure leading to potential oxygen deprivation. Class I recalls, the most severe, are reserved for devices that may cause serious injury or death, as noted in the FDA’s announcement. As of April 14, one death and four injuries have been associated with this device failure.
These ventilators are commonly used in hospitals or under medical supervision for patients who have difficulty regulating breathing on their own. Normally, if oxygen flow is interrupted, the device sounds alarms, alerting supervisors. The failure comes when a power fluctuation causes the device to randomly shut down, which forces the alarm system to reboot. This internal disruption is the reason for the recall.
When the device shuts down out of the blue, it may or may not sound the requisite alarm that would allow providers to intervene. If the device does not sound the alarm, patients may lose oxygen for an extended period, without a provider even knowing.
Philips was notified of these problems and began the recall process on March 10. Currently, it is estimated that 56,671 devices have been distributed throughout the United States. The FDA and Philips Respironics advise that if providers are already using these ventilators, they may continue to do so in accordance with extra set of instructions.
First, customers should connect the device to an external alarm or nurse call system. Second, they should use an external oxygen monitor and a pulse oximeter to keep track of air flow. Finally, if one is available, there should be a backup ventilator on the premises. That way, if there is an interruption in oxygen flow, someone will be alerted and can quickly intervene.
If there is a problem, the patient should be removed from the Philips ventilator and immediately placed on an alternate device. The FDA instructs customers who have experienced problems to report them to its MedWatch database.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has announced a Class I recall for Philips Respironics V60 and V60 Plus ventilators, citing a power failure leading to potential oxygen deprivation. Class I recalls, the most severe, are reserved for devices that may cause serious injury or death, as noted in the FDA’s announcement. As of April 14, one death and four injuries have been associated with this device failure.
These ventilators are commonly used in hospitals or under medical supervision for patients who have difficulty regulating breathing on their own. Normally, if oxygen flow is interrupted, the device sounds alarms, alerting supervisors. The failure comes when a power fluctuation causes the device to randomly shut down, which forces the alarm system to reboot. This internal disruption is the reason for the recall.
When the device shuts down out of the blue, it may or may not sound the requisite alarm that would allow providers to intervene. If the device does not sound the alarm, patients may lose oxygen for an extended period, without a provider even knowing.
Philips was notified of these problems and began the recall process on March 10. Currently, it is estimated that 56,671 devices have been distributed throughout the United States. The FDA and Philips Respironics advise that if providers are already using these ventilators, they may continue to do so in accordance with extra set of instructions.
First, customers should connect the device to an external alarm or nurse call system. Second, they should use an external oxygen monitor and a pulse oximeter to keep track of air flow. Finally, if one is available, there should be a backup ventilator on the premises. That way, if there is an interruption in oxygen flow, someone will be alerted and can quickly intervene.
If there is a problem, the patient should be removed from the Philips ventilator and immediately placed on an alternate device. The FDA instructs customers who have experienced problems to report them to its MedWatch database.
A version of this article first appeared on Medscape.com.
Think it’s ILD? Tell it to the machines
SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.
For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.
“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.
AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
Reading between the lines
In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.
“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.
“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
Putting it together
Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.
“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
AI Spirometry details
In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.
The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.
In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.
The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.
In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.
Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).
There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
Language processing details
Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.
The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.
The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.
For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.
The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).
The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.
SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.
For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.
“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.
AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
Reading between the lines
In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.
“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.
“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
Putting it together
Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.
“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
AI Spirometry details
In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.
The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.
In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.
The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.
In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.
Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).
There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
Language processing details
Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.
The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.
The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.
For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.
The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).
The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.
SAN FRANCISCO – Interstitial lung disease is a difficult diagnosis to make, but a combination of artificial intelligence (AI) techniques and automated language processing could help clinicians identify the early signs of ILD and start patients on therapy, investigators say.
For example, applying an AI algorithm to spirometry readings taken from patients whose data were registered in the UK Biobank identified 27% as having ILD, and of this group, 66% had ostensibly normal lung function on spirometry but were later diagnosed with ILD, reported Marko Topalovic, PhD, from the AI company ArtiQ in Leuven, Belgium, at the American Thoracic Society’s international conference.
“A diagnosis of ILD is very challenging, so you have patients who are going to be misdiagnosed or have a very late diagnosis, so we aimed to apply our AI algorithm on spirometry to see whether we could detect ILD much earlier,” he said in an interview conducted during a poster discussion session.
AI detected ILD up to 6.8 years before a clinician’s diagnosis, Dr. Topalovic said.
Reading between the lines
In a separate study, investigators at the University of California, Davis, used language analysis software to scour electronic health records for words indicative of early ILD, and found that the technique dramatically shortened the median time to a pulmonary referral, compared with historical controls.
“This is a language processing program that can essentially look through the radiology reports and look for the key words that often describe interstitial lung disease, like traction, honeycomb, fibrotic, etc. With those studies being flagged, an actual pulmonologist will then further review the scan, and see whether it meets criteria for one of the interstitial lung diseases,” lead author William Leon, MD, a resident in the department of internal medicine at the University of California, Davis, said in an interview.
“We then sent the primary care doctor a message to say: ‘Hey, this patient has ILD. You need to send them to a pulmonologist,’ ” he added.
Putting it together
Philip L. Molyneaux, MRCP (UK), MBBS, BS (Hons), from Imperial College London, who comoderated the session but was not involved in the studies, speculated that combining these and other, nontechnical interventions also discussed could help to improve diagnosis of ILD and allow clinicians to prescribe therapy earlier in the disease course.
“What’s going to give you the biggest impact for patients? Everyone working individually is coming up with great advances, and if you put them all together it’s going to provide much greater benefit for our patients,” he said in an interview.
AI Spirometry details
In collaboration with colleagues at the Laboratory of Respiratory Disease at University Hospital in Leuven, Dr. Topalovic applied AI to results of spirometry performed prior to diagnosis of ILD among 109 patients registered in the UK Biobank, a repository of information on more than 500,000 volunteers.
The patients selected had ILD listed as their cause of death, had spirometry performed up to 7 years before their deaths, and did not receive a diagnosis of ILD on the day of the index spirometry.
In all 73% of patients were men, 27% women, with an average age of 64.6 years. A large majority of the sample (77.15%) had a history of smoking, and 60 of the patients (55%) died within one year of an ILD diagnosis.
The investigators plugged the spirometry data and each patients demographic information – including gender, age, height, weight, race, and smoking status – into the AI clinical decision support program, which yielded a statistical probability for each subject of having normal lung function, asthma, COPD, ILD, another obstructive disease, or another unidentifiable respiratory disease.
In 29 patients (27%) the software listed ILD as the highest probability, and of this group 19 patients (66%) had normal lung function according to standard interpretation guidelines.
Spirometry parameters among patients identified as having probable ILD were different from those where ILD was not detected. For example, forced vital capacity (FVC) was 76% of predicted among patients with likely ILD versus 87% of predicted in those who had a diagnosis later (P = .003). Similar differences were seen in the forced expiratory volume in 1 second to FVC ratio, at 0.82 vs. 0.75, respectively (P = .007).
There were no differences in mortality or in median time between spirometry and clinician diagnosis between the groups.
Language processing details
Dr. Leon and colleagues used a language analysis software package to review CT chest reports. Reports were flagged if they contained the words traction, honeycomb, fibrotic, fibrosis, reticular, or reticulation.
The CT scan accompanying each flagged reported was reviewed by a pulmonologist for the presence of ILD, and scans with ILD identified were referred to pulmonary specialists. The results of 2,198 prospective scans followed by prospective screening were compared with those of 1,690 historical controls seen in 2015 and 2016.
The investigators found that 85 incident cases of ILD were identified in the historical controls, compared with 143 in the prospective cohort, leading to 38 and 120 pulmonary referrals, respectively.
For the primary outcome of median time from CT to pulmonary referral, the authors found that it was 1.27 months for the prospective cohort, compared with not reached (censored after 18 months) in historical controls.
The hazard ratio for a pulmonary referral in the prospective versus historical cohort was 2.79, an association that was strengthened after adjusting for sex, age, race, smoking pack-years, cough, crackles, and dyspnea (HR, 4.54; both comparisons significant according to confidence intervals).
The studies were internally funded. Dr. Topalovic is CEO and cofounder of ArtiQ. Dr. Leon and Dr. Molyneaux reported no relevant conflicts of interest.
AT ATS 2022