User login
Daily aspirin associated with lower risk of COPD flareup
Daily aspirin use could reduce the risk of acute exacerbations of chronic obstructive pulmonary disease, new data suggest.
Researchers reported the outcomes of an observational cohort study of 1,698 individuals with COPD, 45% of whom said they were taking daily aspirin at baseline. Their findings were published in Chest.
After a median follow up of 2.7 years, aspirin users had an overall 22% lower incidence of acute COPD exacerbations compared with nonusers. This was largely accounted for by a 25% reduction in moderate exacerbations, but there was no significant difference between aspirin users and nonusers in severe exacerbations.
A similar pattern was seen after just 1 year of follow-up, with an overall 30% reduction in the incidence of exacerbations, a 37% reduction in moderate exacerbations, but no significant reduction in severe exacerbations.
“Though aspirin use has previously been linked with reduced mortality risk in patients with COPD, to our knowledge, this is the first study to investigate the association of daily aspirin use with respiratory morbidity in COPD,” wrote Ashraf Fawzy, MD, of the division of pulmonary and critical care medicine at Johns Hopkins University, Baltimore, and his coauthors.
The association between aspirin use and reduced incidence of exacerbations was stronger among individuals with chronic bronchitis, which prompted the authors to suggest that future studies of aspirin in COPD should focus on participants with chronic bronchitis.
However, the association was not affected by COPD severity, emphysema presence or severity, or cardiometabolic phenotype.
Aspirin users reported better respiratory-specific quality of life than that of nonusers, including 34% lower odds of reporting moderate to severe dyspnea, and better baseline COPD health status.
“Findings of this study add to the existing literature by highlighting that aspirin use is also associated with reduced respiratory morbidity across several domains – including exacerbation risk, quality of life, and dyspnea – factors related to patient well-being and healthcare utilization,” the authors wrote.
Aspirin users were more likely to be white, male, and obese, and less likely to be smokers. They had better lung function but more cardiovascular comorbidities at baseline, although the aspirin users and nonusers were matched on baseline characteristics.
Speculating on the mechanisms by which aspirin might impact COPD exacerbations, the authors noted that the drug has both systemic and local pulmonary mechanisms of action.
For example, a pathway that results in elevated levels of a urinary metabolite in patients with COPD is irreversibly blocked by aspirin. Aspirin also attenuates the elevation of inflammatory markers interleukin-6 and C-reactive protein, which are part of the inflammatory phenotype of COPD. Aspirin has been shown to reduce proinflammatory cytokines in the lung.
The authors did note that aspirin use was self-reported, so they did not have data on dosage or duration of use.
The National Institutes of Health funded the study. Six authors declared advisory board positions, research support, and other funding from the pharmaceutical sector. One author was also a founder of a company commercializing lung image analysis software. No other conflicts of interest were declared.
SOURCE: Fawzy A et al. Chest. 2019 Mar;155(3): 519-27. doi: 10.1016/j.chest.2018.11.028.
Daily aspirin use could reduce the risk of acute exacerbations of chronic obstructive pulmonary disease, new data suggest.
Researchers reported the outcomes of an observational cohort study of 1,698 individuals with COPD, 45% of whom said they were taking daily aspirin at baseline. Their findings were published in Chest.
After a median follow up of 2.7 years, aspirin users had an overall 22% lower incidence of acute COPD exacerbations compared with nonusers. This was largely accounted for by a 25% reduction in moderate exacerbations, but there was no significant difference between aspirin users and nonusers in severe exacerbations.
A similar pattern was seen after just 1 year of follow-up, with an overall 30% reduction in the incidence of exacerbations, a 37% reduction in moderate exacerbations, but no significant reduction in severe exacerbations.
“Though aspirin use has previously been linked with reduced mortality risk in patients with COPD, to our knowledge, this is the first study to investigate the association of daily aspirin use with respiratory morbidity in COPD,” wrote Ashraf Fawzy, MD, of the division of pulmonary and critical care medicine at Johns Hopkins University, Baltimore, and his coauthors.
The association between aspirin use and reduced incidence of exacerbations was stronger among individuals with chronic bronchitis, which prompted the authors to suggest that future studies of aspirin in COPD should focus on participants with chronic bronchitis.
However, the association was not affected by COPD severity, emphysema presence or severity, or cardiometabolic phenotype.
Aspirin users reported better respiratory-specific quality of life than that of nonusers, including 34% lower odds of reporting moderate to severe dyspnea, and better baseline COPD health status.
“Findings of this study add to the existing literature by highlighting that aspirin use is also associated with reduced respiratory morbidity across several domains – including exacerbation risk, quality of life, and dyspnea – factors related to patient well-being and healthcare utilization,” the authors wrote.
Aspirin users were more likely to be white, male, and obese, and less likely to be smokers. They had better lung function but more cardiovascular comorbidities at baseline, although the aspirin users and nonusers were matched on baseline characteristics.
Speculating on the mechanisms by which aspirin might impact COPD exacerbations, the authors noted that the drug has both systemic and local pulmonary mechanisms of action.
For example, a pathway that results in elevated levels of a urinary metabolite in patients with COPD is irreversibly blocked by aspirin. Aspirin also attenuates the elevation of inflammatory markers interleukin-6 and C-reactive protein, which are part of the inflammatory phenotype of COPD. Aspirin has been shown to reduce proinflammatory cytokines in the lung.
The authors did note that aspirin use was self-reported, so they did not have data on dosage or duration of use.
The National Institutes of Health funded the study. Six authors declared advisory board positions, research support, and other funding from the pharmaceutical sector. One author was also a founder of a company commercializing lung image analysis software. No other conflicts of interest were declared.
SOURCE: Fawzy A et al. Chest. 2019 Mar;155(3): 519-27. doi: 10.1016/j.chest.2018.11.028.
Daily aspirin use could reduce the risk of acute exacerbations of chronic obstructive pulmonary disease, new data suggest.
Researchers reported the outcomes of an observational cohort study of 1,698 individuals with COPD, 45% of whom said they were taking daily aspirin at baseline. Their findings were published in Chest.
After a median follow up of 2.7 years, aspirin users had an overall 22% lower incidence of acute COPD exacerbations compared with nonusers. This was largely accounted for by a 25% reduction in moderate exacerbations, but there was no significant difference between aspirin users and nonusers in severe exacerbations.
A similar pattern was seen after just 1 year of follow-up, with an overall 30% reduction in the incidence of exacerbations, a 37% reduction in moderate exacerbations, but no significant reduction in severe exacerbations.
“Though aspirin use has previously been linked with reduced mortality risk in patients with COPD, to our knowledge, this is the first study to investigate the association of daily aspirin use with respiratory morbidity in COPD,” wrote Ashraf Fawzy, MD, of the division of pulmonary and critical care medicine at Johns Hopkins University, Baltimore, and his coauthors.
The association between aspirin use and reduced incidence of exacerbations was stronger among individuals with chronic bronchitis, which prompted the authors to suggest that future studies of aspirin in COPD should focus on participants with chronic bronchitis.
However, the association was not affected by COPD severity, emphysema presence or severity, or cardiometabolic phenotype.
Aspirin users reported better respiratory-specific quality of life than that of nonusers, including 34% lower odds of reporting moderate to severe dyspnea, and better baseline COPD health status.
“Findings of this study add to the existing literature by highlighting that aspirin use is also associated with reduced respiratory morbidity across several domains – including exacerbation risk, quality of life, and dyspnea – factors related to patient well-being and healthcare utilization,” the authors wrote.
Aspirin users were more likely to be white, male, and obese, and less likely to be smokers. They had better lung function but more cardiovascular comorbidities at baseline, although the aspirin users and nonusers were matched on baseline characteristics.
Speculating on the mechanisms by which aspirin might impact COPD exacerbations, the authors noted that the drug has both systemic and local pulmonary mechanisms of action.
For example, a pathway that results in elevated levels of a urinary metabolite in patients with COPD is irreversibly blocked by aspirin. Aspirin also attenuates the elevation of inflammatory markers interleukin-6 and C-reactive protein, which are part of the inflammatory phenotype of COPD. Aspirin has been shown to reduce proinflammatory cytokines in the lung.
The authors did note that aspirin use was self-reported, so they did not have data on dosage or duration of use.
The National Institutes of Health funded the study. Six authors declared advisory board positions, research support, and other funding from the pharmaceutical sector. One author was also a founder of a company commercializing lung image analysis software. No other conflicts of interest were declared.
SOURCE: Fawzy A et al. Chest. 2019 Mar;155(3): 519-27. doi: 10.1016/j.chest.2018.11.028.
FROM CHEST
Poor COPD management might increase MI risk in HIV
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.
Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.
The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.
The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.
COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).
The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.
The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.
“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.
The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.
“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.
The National Institutes of Health funded the work. Dr. Crothers had no disclosures.
SOURCE: Crothers K et al. CROI 2019, Abstract 31.
REPORTING FROM CROI 2019
E-cigarettes beat nicotine patch for smoking cessation
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The rate of smokers who continued to use e-cigarettes after 1 year was “fairly high,” which might be problematic.
Major finding: Abstinence from smoking at 52 weeks was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001).
Study details: Randomized study of 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service.
Disclosures: Dr. Hajek reported grants and fees from Pfizer unrelated to the present study.The coauthors reported disclosures related to Pfizer, and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
Source: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
Five steering committees examine the literature
Airways Disorders
Defining and treating early COPD: Can we make a difference?
There is growing evidence that early COPD—before currently accepted spirometric or symptomatic criteria are present—may be an important clinical entity. The primary pathobiologic mechanisms in early COPD development include both abnormal lung development and accelerated lung aging (Augustí et al. Am J Respir Crit Care Med. 2018 Oct 15;198:8:978).
Martinez and colleagues recently proposed defining early COPD as age <50 with 10+ pack-year smoking history and at least one of the following: (1) early airflow limitation (postbronchodilator FEV1/FVC < lower limit of normal), (2) compatible CT scan abnormalities, (3) rapid decline in FEV1 (≥60 mL/yr) that is accelerated relative to FVC (Martinez et al. Am J Respir Crit Care Med. 2018 Jun 15;197[12]:1540).
A novel multiresolution CT scan imaging protocol described by Koo and coworkers found that substantial loss of small airways— specifically the terminal and transitional bronchioles—occurs in patients with mild-to-moderate COPD even prior to the development of emphysema on CT scan. These findings show that significant destruction of the small airways has occurred prior to the development of mild COPD (Koo et al. Lancet Respir Med. 2018 Aug;6:591).
Pharmacologic treatment for COPD is targeted at the reduction of symptoms and risk of exacerbation, as there remains no conclusive evidence that existing therapies modify long-term decline in lung function. It is unknown if pharmacotherapy for “early COPD” will alter the disease course. While not directly addressing this subset, information may be gleaned from trials on younger, more mild GOLD Stage 1 or Stage 2 patients. The Tie-COPD trial, the largest powered study to date of mild-to-moderate COPD, found that among patients with GOLD stage 1 or 2 COPD treatment with tiotropium compared with placebo for 2 years resulted in significantly higher FEV1 before bronchodilator use (between group difference of 157 mL) and slowed annual decline in FEV1 after bronchodilator use (Zhou et al. N Engl J Med. 2017 Sep 7;377[10]:923).
As our understanding of heterogeneity within COPD increases, striving for improved outcomes from our therapies—an impact on lung function in addition to symptom and exacerbation risk—may need to begin with the study of earlier treatment.
Megan Conroy, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, DO, FCCP
Steering Committee Vice-Chair
Clinical Pulmonary Medicine
Asthma-COPD overlap: An underappreciated phenotype of obstructive airway disease (OAD)
Asthma-COPD overlap (ACO) is a common yet underappreciated clinical entity within the complex OAD spectrum. Currently, there is no consensus criteria to define ACO; however, a roundtable consensus from an international group (Sin et al. Eur Respir J. 2016 Sep;48:664) suggests using major and minor criteria, with key features being airflow limitation, asthma history, and cigarette or biomass exposure. Several studies have shown that patients with ACO have severe disease, faster lung function decline, greater morbidity and mortality, and lower QoL (Alshabanat et al. PLoS One. 2015 Sep 3;10:e0136065).
There is paucity of data on the pathophysiology, risk factors, and clinical management given exclusion of these patients from clinical trials of asthma and COPD. Indeed, clinicians and researchers now realize that ACO is an umbrella term for multiple subphenotypes, including patients who have predominant asthma with some COPD features and others with predominant COPD with some asthma features. Overall, IgE level, FeNO, sputum, and blood eosinophils are usually higher in ACO than in COPD and relatively similar compared with asthma (Kobayashi et al. Int J Chron Obs Pulmon Dis. 2016 May 26;11:2117).
Most recently, a longitudinal study looked at predictors of ACO among NY firefighters exposed to WTC dust (Singh et al. CHEST. 2018 Dec;154[6]:1301). Pre-exposure low lung function and elevated blood eosinophils and IL4 (T2 inflammatory cytokine) increased risk of developing ACO among those exposed to WTC dust. Further research is required to better understand the interaction of environmental exposure and risk factors in the pathophysiology of ACO. It may be more pragmatic to use the unifying term OAD, as originally proposed in the Dutch hypothesis, and further delineate how several phenotypes of airway disease can be classified by combining traditional approaches with molecular and genomic analysis.
Munish Luthra, MD, FCCP
Steering Committee Member
Samantha D’Annunzio, MD
Steering Committee Member
Critical Care
Mechanical ventilation: One size fits all?
Mechanical ventilation (MV) is a lifesaving intervention in the ICU, but it has been associated with numerous complications ranging from overuse of sedation, atelectasis, and baro or volutrauma.
After 2000, it became well known that using a low tidal volume (VT) strategy (6 mL/kg predicted body weight, PBW) in patients with ARDS produced lower mortality and more ventilator-free days (N Engl J Med. 2000 May 4;342[18]:1301). In addition, a meta-analysis in 2012 demonstrated a lower relative risk of new lung injury, mortality, and pulmonary infections with low VT in non-ARDS patients (Serpa et al. JAMA. 2012 Oct 24/31;308[16]:1651). However, the included studies varied widely in their use of VT (9-12 mL/kg), duration of MV, and in mixed settings (ICU or operating room).
Recently, a large randomized clinical trial compared the effect of low (4-6 mL/kg, PBW) vs intermediate (8-10 mL/kg, PBW) VT ventilation strategy in non-ARDS ICU patients. Interestingly, the study concluded that there is no significant difference in ventilator-free days (21 days in each group), median length ICU and hospital stay, ICU mortality rates, and 28- and 90-day mortality. Also, there was no difference in new-onset ARDS, severe atelectasis, sedation use, and delirium (JAMA. 2018; 320[18]:1872). This study suggests that in non-ARDS patients, MV should be individualized according to each patient’s clinical situation, the nature of the disease, and its effect on lung mechanics, especially in patients who cannot tolerate low tidal volumes.
Margaret A. Disselkamp, MD
Steering Committee Member
Mohammed A. Megri, MD
Fellow-in-Training Steering Committee Member
Home-Based Mechanical Ventilation and Neuromuscular Disease
Improving access to sleep medicine care for patients with NMD
Sleep-disordered breathing (SDB) occurs in up to 5% of children, with adverse implications for growth and development. Children with neuromuscular disease are at significantly higher risk than unaffected children (Chiang et al. Children. 2018;5:e78). Respiratory dysfunction that may present as SDB before daytime impairment in gas exchange is evident. Diagnosing and treating SDB (to include OSA, CSA, and hypoventilation syndromes) early can significantly improve morbidity and mortality.
Unfortunately, diagnostic sleep medicine resources are limited. Children may wait up to a year or more for definitive testing with in-laboratory, attended polysomnography (PSG). Among children with neuromuscular disease, fewer than 10% may undergo a sleep clinic evaluation, and, of those that do, they may have only one visit over a 3-year period of care (Rose et al. Pediatr Pulmonol. 2018 Oct;53:1378). Home sleep testing (HST) has been evaluated as an alternative to PSG given lower cost, availability, and advantage of the child sleeping in his/her own bed. Although HST is indicated in adults with a high pretest probability for moderate to severe OSA, it is not indicated in children, given the potential to underestimate disease severity or to miss the diagnosis entirely (Kirk et al. J Clin Sleep Med. 2017 Oct 15;13[10]:1199). HST lacks electroencephalogram (EEG) and capnography. Technical recording mishaps are more common in children, but in-lab PSG has the advantage of on-site troubleshooting by a technologist.
A recently published study by Fishman and colleagues attempted to compare gold standard in-lab PSG to HST with capnography (Fishman et al. J Clin Sleep Med. 2018 Dec 15;14[12]:2013). Despite a well-designed study with a carefully selected population, HST failed to reliably diagnose SDB. HST underestimated disease severity and, in some cases, missed the diagnosis of SDB entirely. The addition of end tidal CO2 monitoring failed to improve diagnostic accuracy, and HST and PSG-ETco2 values were poorly correlated.
Although children with neuromuscular disease face long wait times for sleep evaluations, HST is clearly not the solution for now. It remains to be seen if innovations in HST with extended monitoring (and transcutaneous CO2) become viable. In the meantime, finding ways to improve access to sleep medicine care for children with neuromuscular disease is a must.
Jacob Collen, MD, FCCP
Steering Committee Member
Interstitial and Diffuse Lung Disease
Idiopathic pneumonias that are not all that idiopathic
Despite being defined as an individual entity for research purposes in 2015 (Fisher et al. Eur Respir J. 2015;46:976), interstitial pneumonias with autoimmune features (IPAF) remain a heterogeneous group of interstitial lung diseases that puzzle the clinician. Since the introduction of the IPAF definition, there have been attempts to validate the diagnostic criteria and study their prognostic implications. Some of these studies showed differential prognosis in patients who met the IPAF criteria (Oldham et al. Eur Respir J. 2016;47:1767).
Although the implications of the presence of autoimmune antibodies in idiopathic interstitial pneumonias (IIPs) is not fully understood, the treatment often entails immunosuppression, especially in those with non-UIP patterns of disease and/or clinical features of autoimmune disease. The stakes are high when IIPs are associated with antibodies correlated with rapidly progressive disease, such as MDA-5 antibody or antisynthetase antibodies. Pulmonologists often lack the clinical expertise to detect occult autoimmune disorders, though the role of the rheumatologist in facilitating the diagnosis and treatment of IPAF is not well delineated. Most health-care systems are not equipped with collaborative ILD-rheumatology clinics or even easy access to a rheumatologist. There is a need for real-world pragmatic studies to establish the optimal way to evaluate patients with ILD for autoimmune features and identify patients who would benefit most from an early referral to rheumatology to aid with diagnosis, treatment, and sometimes monitoring for extrapulmonary manifestations of autoimmune disorders.
Avanthika Thanushi Wynn, MD
Steering Committee Fellow-in-Training
Airways Disorders
Defining and treating early COPD: Can we make a difference?
There is growing evidence that early COPD—before currently accepted spirometric or symptomatic criteria are present—may be an important clinical entity. The primary pathobiologic mechanisms in early COPD development include both abnormal lung development and accelerated lung aging (Augustí et al. Am J Respir Crit Care Med. 2018 Oct 15;198:8:978).
Martinez and colleagues recently proposed defining early COPD as age <50 with 10+ pack-year smoking history and at least one of the following: (1) early airflow limitation (postbronchodilator FEV1/FVC < lower limit of normal), (2) compatible CT scan abnormalities, (3) rapid decline in FEV1 (≥60 mL/yr) that is accelerated relative to FVC (Martinez et al. Am J Respir Crit Care Med. 2018 Jun 15;197[12]:1540).
A novel multiresolution CT scan imaging protocol described by Koo and coworkers found that substantial loss of small airways— specifically the terminal and transitional bronchioles—occurs in patients with mild-to-moderate COPD even prior to the development of emphysema on CT scan. These findings show that significant destruction of the small airways has occurred prior to the development of mild COPD (Koo et al. Lancet Respir Med. 2018 Aug;6:591).
Pharmacologic treatment for COPD is targeted at the reduction of symptoms and risk of exacerbation, as there remains no conclusive evidence that existing therapies modify long-term decline in lung function. It is unknown if pharmacotherapy for “early COPD” will alter the disease course. While not directly addressing this subset, information may be gleaned from trials on younger, more mild GOLD Stage 1 or Stage 2 patients. The Tie-COPD trial, the largest powered study to date of mild-to-moderate COPD, found that among patients with GOLD stage 1 or 2 COPD treatment with tiotropium compared with placebo for 2 years resulted in significantly higher FEV1 before bronchodilator use (between group difference of 157 mL) and slowed annual decline in FEV1 after bronchodilator use (Zhou et al. N Engl J Med. 2017 Sep 7;377[10]:923).
As our understanding of heterogeneity within COPD increases, striving for improved outcomes from our therapies—an impact on lung function in addition to symptom and exacerbation risk—may need to begin with the study of earlier treatment.
Megan Conroy, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, DO, FCCP
Steering Committee Vice-Chair
Clinical Pulmonary Medicine
Asthma-COPD overlap: An underappreciated phenotype of obstructive airway disease (OAD)
Asthma-COPD overlap (ACO) is a common yet underappreciated clinical entity within the complex OAD spectrum. Currently, there is no consensus criteria to define ACO; however, a roundtable consensus from an international group (Sin et al. Eur Respir J. 2016 Sep;48:664) suggests using major and minor criteria, with key features being airflow limitation, asthma history, and cigarette or biomass exposure. Several studies have shown that patients with ACO have severe disease, faster lung function decline, greater morbidity and mortality, and lower QoL (Alshabanat et al. PLoS One. 2015 Sep 3;10:e0136065).
There is paucity of data on the pathophysiology, risk factors, and clinical management given exclusion of these patients from clinical trials of asthma and COPD. Indeed, clinicians and researchers now realize that ACO is an umbrella term for multiple subphenotypes, including patients who have predominant asthma with some COPD features and others with predominant COPD with some asthma features. Overall, IgE level, FeNO, sputum, and blood eosinophils are usually higher in ACO than in COPD and relatively similar compared with asthma (Kobayashi et al. Int J Chron Obs Pulmon Dis. 2016 May 26;11:2117).
Most recently, a longitudinal study looked at predictors of ACO among NY firefighters exposed to WTC dust (Singh et al. CHEST. 2018 Dec;154[6]:1301). Pre-exposure low lung function and elevated blood eosinophils and IL4 (T2 inflammatory cytokine) increased risk of developing ACO among those exposed to WTC dust. Further research is required to better understand the interaction of environmental exposure and risk factors in the pathophysiology of ACO. It may be more pragmatic to use the unifying term OAD, as originally proposed in the Dutch hypothesis, and further delineate how several phenotypes of airway disease can be classified by combining traditional approaches with molecular and genomic analysis.
Munish Luthra, MD, FCCP
Steering Committee Member
Samantha D’Annunzio, MD
Steering Committee Member
Critical Care
Mechanical ventilation: One size fits all?
Mechanical ventilation (MV) is a lifesaving intervention in the ICU, but it has been associated with numerous complications ranging from overuse of sedation, atelectasis, and baro or volutrauma.
After 2000, it became well known that using a low tidal volume (VT) strategy (6 mL/kg predicted body weight, PBW) in patients with ARDS produced lower mortality and more ventilator-free days (N Engl J Med. 2000 May 4;342[18]:1301). In addition, a meta-analysis in 2012 demonstrated a lower relative risk of new lung injury, mortality, and pulmonary infections with low VT in non-ARDS patients (Serpa et al. JAMA. 2012 Oct 24/31;308[16]:1651). However, the included studies varied widely in their use of VT (9-12 mL/kg), duration of MV, and in mixed settings (ICU or operating room).
Recently, a large randomized clinical trial compared the effect of low (4-6 mL/kg, PBW) vs intermediate (8-10 mL/kg, PBW) VT ventilation strategy in non-ARDS ICU patients. Interestingly, the study concluded that there is no significant difference in ventilator-free days (21 days in each group), median length ICU and hospital stay, ICU mortality rates, and 28- and 90-day mortality. Also, there was no difference in new-onset ARDS, severe atelectasis, sedation use, and delirium (JAMA. 2018; 320[18]:1872). This study suggests that in non-ARDS patients, MV should be individualized according to each patient’s clinical situation, the nature of the disease, and its effect on lung mechanics, especially in patients who cannot tolerate low tidal volumes.
Margaret A. Disselkamp, MD
Steering Committee Member
Mohammed A. Megri, MD
Fellow-in-Training Steering Committee Member
Home-Based Mechanical Ventilation and Neuromuscular Disease
Improving access to sleep medicine care for patients with NMD
Sleep-disordered breathing (SDB) occurs in up to 5% of children, with adverse implications for growth and development. Children with neuromuscular disease are at significantly higher risk than unaffected children (Chiang et al. Children. 2018;5:e78). Respiratory dysfunction that may present as SDB before daytime impairment in gas exchange is evident. Diagnosing and treating SDB (to include OSA, CSA, and hypoventilation syndromes) early can significantly improve morbidity and mortality.
Unfortunately, diagnostic sleep medicine resources are limited. Children may wait up to a year or more for definitive testing with in-laboratory, attended polysomnography (PSG). Among children with neuromuscular disease, fewer than 10% may undergo a sleep clinic evaluation, and, of those that do, they may have only one visit over a 3-year period of care (Rose et al. Pediatr Pulmonol. 2018 Oct;53:1378). Home sleep testing (HST) has been evaluated as an alternative to PSG given lower cost, availability, and advantage of the child sleeping in his/her own bed. Although HST is indicated in adults with a high pretest probability for moderate to severe OSA, it is not indicated in children, given the potential to underestimate disease severity or to miss the diagnosis entirely (Kirk et al. J Clin Sleep Med. 2017 Oct 15;13[10]:1199). HST lacks electroencephalogram (EEG) and capnography. Technical recording mishaps are more common in children, but in-lab PSG has the advantage of on-site troubleshooting by a technologist.
A recently published study by Fishman and colleagues attempted to compare gold standard in-lab PSG to HST with capnography (Fishman et al. J Clin Sleep Med. 2018 Dec 15;14[12]:2013). Despite a well-designed study with a carefully selected population, HST failed to reliably diagnose SDB. HST underestimated disease severity and, in some cases, missed the diagnosis of SDB entirely. The addition of end tidal CO2 monitoring failed to improve diagnostic accuracy, and HST and PSG-ETco2 values were poorly correlated.
Although children with neuromuscular disease face long wait times for sleep evaluations, HST is clearly not the solution for now. It remains to be seen if innovations in HST with extended monitoring (and transcutaneous CO2) become viable. In the meantime, finding ways to improve access to sleep medicine care for children with neuromuscular disease is a must.
Jacob Collen, MD, FCCP
Steering Committee Member
Interstitial and Diffuse Lung Disease
Idiopathic pneumonias that are not all that idiopathic
Despite being defined as an individual entity for research purposes in 2015 (Fisher et al. Eur Respir J. 2015;46:976), interstitial pneumonias with autoimmune features (IPAF) remain a heterogeneous group of interstitial lung diseases that puzzle the clinician. Since the introduction of the IPAF definition, there have been attempts to validate the diagnostic criteria and study their prognostic implications. Some of these studies showed differential prognosis in patients who met the IPAF criteria (Oldham et al. Eur Respir J. 2016;47:1767).
Although the implications of the presence of autoimmune antibodies in idiopathic interstitial pneumonias (IIPs) is not fully understood, the treatment often entails immunosuppression, especially in those with non-UIP patterns of disease and/or clinical features of autoimmune disease. The stakes are high when IIPs are associated with antibodies correlated with rapidly progressive disease, such as MDA-5 antibody or antisynthetase antibodies. Pulmonologists often lack the clinical expertise to detect occult autoimmune disorders, though the role of the rheumatologist in facilitating the diagnosis and treatment of IPAF is not well delineated. Most health-care systems are not equipped with collaborative ILD-rheumatology clinics or even easy access to a rheumatologist. There is a need for real-world pragmatic studies to establish the optimal way to evaluate patients with ILD for autoimmune features and identify patients who would benefit most from an early referral to rheumatology to aid with diagnosis, treatment, and sometimes monitoring for extrapulmonary manifestations of autoimmune disorders.
Avanthika Thanushi Wynn, MD
Steering Committee Fellow-in-Training
Airways Disorders
Defining and treating early COPD: Can we make a difference?
There is growing evidence that early COPD—before currently accepted spirometric or symptomatic criteria are present—may be an important clinical entity. The primary pathobiologic mechanisms in early COPD development include both abnormal lung development and accelerated lung aging (Augustí et al. Am J Respir Crit Care Med. 2018 Oct 15;198:8:978).
Martinez and colleagues recently proposed defining early COPD as age <50 with 10+ pack-year smoking history and at least one of the following: (1) early airflow limitation (postbronchodilator FEV1/FVC < lower limit of normal), (2) compatible CT scan abnormalities, (3) rapid decline in FEV1 (≥60 mL/yr) that is accelerated relative to FVC (Martinez et al. Am J Respir Crit Care Med. 2018 Jun 15;197[12]:1540).
A novel multiresolution CT scan imaging protocol described by Koo and coworkers found that substantial loss of small airways— specifically the terminal and transitional bronchioles—occurs in patients with mild-to-moderate COPD even prior to the development of emphysema on CT scan. These findings show that significant destruction of the small airways has occurred prior to the development of mild COPD (Koo et al. Lancet Respir Med. 2018 Aug;6:591).
Pharmacologic treatment for COPD is targeted at the reduction of symptoms and risk of exacerbation, as there remains no conclusive evidence that existing therapies modify long-term decline in lung function. It is unknown if pharmacotherapy for “early COPD” will alter the disease course. While not directly addressing this subset, information may be gleaned from trials on younger, more mild GOLD Stage 1 or Stage 2 patients. The Tie-COPD trial, the largest powered study to date of mild-to-moderate COPD, found that among patients with GOLD stage 1 or 2 COPD treatment with tiotropium compared with placebo for 2 years resulted in significantly higher FEV1 before bronchodilator use (between group difference of 157 mL) and slowed annual decline in FEV1 after bronchodilator use (Zhou et al. N Engl J Med. 2017 Sep 7;377[10]:923).
As our understanding of heterogeneity within COPD increases, striving for improved outcomes from our therapies—an impact on lung function in addition to symptom and exacerbation risk—may need to begin with the study of earlier treatment.
Megan Conroy, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, DO, FCCP
Steering Committee Vice-Chair
Clinical Pulmonary Medicine
Asthma-COPD overlap: An underappreciated phenotype of obstructive airway disease (OAD)
Asthma-COPD overlap (ACO) is a common yet underappreciated clinical entity within the complex OAD spectrum. Currently, there is no consensus criteria to define ACO; however, a roundtable consensus from an international group (Sin et al. Eur Respir J. 2016 Sep;48:664) suggests using major and minor criteria, with key features being airflow limitation, asthma history, and cigarette or biomass exposure. Several studies have shown that patients with ACO have severe disease, faster lung function decline, greater morbidity and mortality, and lower QoL (Alshabanat et al. PLoS One. 2015 Sep 3;10:e0136065).
There is paucity of data on the pathophysiology, risk factors, and clinical management given exclusion of these patients from clinical trials of asthma and COPD. Indeed, clinicians and researchers now realize that ACO is an umbrella term for multiple subphenotypes, including patients who have predominant asthma with some COPD features and others with predominant COPD with some asthma features. Overall, IgE level, FeNO, sputum, and blood eosinophils are usually higher in ACO than in COPD and relatively similar compared with asthma (Kobayashi et al. Int J Chron Obs Pulmon Dis. 2016 May 26;11:2117).
Most recently, a longitudinal study looked at predictors of ACO among NY firefighters exposed to WTC dust (Singh et al. CHEST. 2018 Dec;154[6]:1301). Pre-exposure low lung function and elevated blood eosinophils and IL4 (T2 inflammatory cytokine) increased risk of developing ACO among those exposed to WTC dust. Further research is required to better understand the interaction of environmental exposure and risk factors in the pathophysiology of ACO. It may be more pragmatic to use the unifying term OAD, as originally proposed in the Dutch hypothesis, and further delineate how several phenotypes of airway disease can be classified by combining traditional approaches with molecular and genomic analysis.
Munish Luthra, MD, FCCP
Steering Committee Member
Samantha D’Annunzio, MD
Steering Committee Member
Critical Care
Mechanical ventilation: One size fits all?
Mechanical ventilation (MV) is a lifesaving intervention in the ICU, but it has been associated with numerous complications ranging from overuse of sedation, atelectasis, and baro or volutrauma.
After 2000, it became well known that using a low tidal volume (VT) strategy (6 mL/kg predicted body weight, PBW) in patients with ARDS produced lower mortality and more ventilator-free days (N Engl J Med. 2000 May 4;342[18]:1301). In addition, a meta-analysis in 2012 demonstrated a lower relative risk of new lung injury, mortality, and pulmonary infections with low VT in non-ARDS patients (Serpa et al. JAMA. 2012 Oct 24/31;308[16]:1651). However, the included studies varied widely in their use of VT (9-12 mL/kg), duration of MV, and in mixed settings (ICU or operating room).
Recently, a large randomized clinical trial compared the effect of low (4-6 mL/kg, PBW) vs intermediate (8-10 mL/kg, PBW) VT ventilation strategy in non-ARDS ICU patients. Interestingly, the study concluded that there is no significant difference in ventilator-free days (21 days in each group), median length ICU and hospital stay, ICU mortality rates, and 28- and 90-day mortality. Also, there was no difference in new-onset ARDS, severe atelectasis, sedation use, and delirium (JAMA. 2018; 320[18]:1872). This study suggests that in non-ARDS patients, MV should be individualized according to each patient’s clinical situation, the nature of the disease, and its effect on lung mechanics, especially in patients who cannot tolerate low tidal volumes.
Margaret A. Disselkamp, MD
Steering Committee Member
Mohammed A. Megri, MD
Fellow-in-Training Steering Committee Member
Home-Based Mechanical Ventilation and Neuromuscular Disease
Improving access to sleep medicine care for patients with NMD
Sleep-disordered breathing (SDB) occurs in up to 5% of children, with adverse implications for growth and development. Children with neuromuscular disease are at significantly higher risk than unaffected children (Chiang et al. Children. 2018;5:e78). Respiratory dysfunction that may present as SDB before daytime impairment in gas exchange is evident. Diagnosing and treating SDB (to include OSA, CSA, and hypoventilation syndromes) early can significantly improve morbidity and mortality.
Unfortunately, diagnostic sleep medicine resources are limited. Children may wait up to a year or more for definitive testing with in-laboratory, attended polysomnography (PSG). Among children with neuromuscular disease, fewer than 10% may undergo a sleep clinic evaluation, and, of those that do, they may have only one visit over a 3-year period of care (Rose et al. Pediatr Pulmonol. 2018 Oct;53:1378). Home sleep testing (HST) has been evaluated as an alternative to PSG given lower cost, availability, and advantage of the child sleeping in his/her own bed. Although HST is indicated in adults with a high pretest probability for moderate to severe OSA, it is not indicated in children, given the potential to underestimate disease severity or to miss the diagnosis entirely (Kirk et al. J Clin Sleep Med. 2017 Oct 15;13[10]:1199). HST lacks electroencephalogram (EEG) and capnography. Technical recording mishaps are more common in children, but in-lab PSG has the advantage of on-site troubleshooting by a technologist.
A recently published study by Fishman and colleagues attempted to compare gold standard in-lab PSG to HST with capnography (Fishman et al. J Clin Sleep Med. 2018 Dec 15;14[12]:2013). Despite a well-designed study with a carefully selected population, HST failed to reliably diagnose SDB. HST underestimated disease severity and, in some cases, missed the diagnosis of SDB entirely. The addition of end tidal CO2 monitoring failed to improve diagnostic accuracy, and HST and PSG-ETco2 values were poorly correlated.
Although children with neuromuscular disease face long wait times for sleep evaluations, HST is clearly not the solution for now. It remains to be seen if innovations in HST with extended monitoring (and transcutaneous CO2) become viable. In the meantime, finding ways to improve access to sleep medicine care for children with neuromuscular disease is a must.
Jacob Collen, MD, FCCP
Steering Committee Member
Interstitial and Diffuse Lung Disease
Idiopathic pneumonias that are not all that idiopathic
Despite being defined as an individual entity for research purposes in 2015 (Fisher et al. Eur Respir J. 2015;46:976), interstitial pneumonias with autoimmune features (IPAF) remain a heterogeneous group of interstitial lung diseases that puzzle the clinician. Since the introduction of the IPAF definition, there have been attempts to validate the diagnostic criteria and study their prognostic implications. Some of these studies showed differential prognosis in patients who met the IPAF criteria (Oldham et al. Eur Respir J. 2016;47:1767).
Although the implications of the presence of autoimmune antibodies in idiopathic interstitial pneumonias (IIPs) is not fully understood, the treatment often entails immunosuppression, especially in those with non-UIP patterns of disease and/or clinical features of autoimmune disease. The stakes are high when IIPs are associated with antibodies correlated with rapidly progressive disease, such as MDA-5 antibody or antisynthetase antibodies. Pulmonologists often lack the clinical expertise to detect occult autoimmune disorders, though the role of the rheumatologist in facilitating the diagnosis and treatment of IPAF is not well delineated. Most health-care systems are not equipped with collaborative ILD-rheumatology clinics or even easy access to a rheumatologist. There is a need for real-world pragmatic studies to establish the optimal way to evaluate patients with ILD for autoimmune features and identify patients who would benefit most from an early referral to rheumatology to aid with diagnosis, treatment, and sometimes monitoring for extrapulmonary manifestations of autoimmune disorders.
Avanthika Thanushi Wynn, MD
Steering Committee Fellow-in-Training
FDA approves generic Advair Diskus
The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.
The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.
Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.
This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”
Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.
The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.
The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.
Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.
This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”
Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.
The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.
The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.
Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.
This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”
Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.
COPD linked to higher in-hospital death rates in patients with PAD
A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.
This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.
“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”
Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.
The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.
In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).
Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.
“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.
Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”
The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.
SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.
A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.
This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.
“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”
Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.
The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.
In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).
Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.
“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.
Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”
The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.
SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.
A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.
This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.
“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”
Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.
The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.
In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).
Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.
“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.
Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”
The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.
SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.
FROM RESPIRATORY MEDICINE
Key clinical point:
Major finding: All-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without (6.5% vs. 4.7%; P less than 0.001).
Study details: Database analysis of 5.6 million German PAD inpatients stratified for COPD.
Disclosures: The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.
Source: Keller K et al. Respir Med. 2019 Feb;147:1-6.
Biomarkers predict asthma/COPD risk in 9/11 first responders
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
FROM CHEST
Key clinical point: Firefighters exposed to toxins at the World Trade Center on 9/11 who demonstrated elevated blood eosinophils and IL-4 levels were at increased risk for subsequent asthma/chronic obstructive pulmonary disease overlap.
Major finding: Increased eosinophils (300 cells/mcL or higher) was significantly associated with asthma/chronic obstructive pulmonary disease overlap (hazard ratio, 1.85).
Study details: The data come from 2,137 firefighters exposed to toxins at the World Trade Center in New York on 9/11.
Disclosures: The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
Source: Singh A et al. CHEST. 2018 Dec; 154;1301-10.
Non-TB mycobacteria infections rising in COPD patients
Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.
For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.
Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.
Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.
The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.
Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.
Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.
SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.
Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.
For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.
Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.
Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.
The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.
Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.
Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.
SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.
Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.
For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.
Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.
Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.
The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.
Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.
Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.
SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.
FROM FRONTIERS IN MEDICINE
Key clinical point: Incidence and prevalence of non-TB mycobacteria infections rose sharply in a national veterans population with chronic obstructive pulmonary disease after 2012.
Major finding: Incidence of non-TB mycobacteria infections doubled in chronic obstructive pulmonary disease patients between 2001 and 2015, with most of the increase seen after 2012
Study details: A retrospective, cross-sectional study using records from over 2 million, mostly male chronic obstructive pulmonary disease patients in a Veterans Affairs database.
Disclosures: The study authors reported no outside sources of funding or financial conflicts of interest.
Source: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.
FDA approves Yupelri for COPD maintenance therapy
The Food and Drug Administration has approved Yupelri (revefenacin) for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD).
Revefenacin is a long-acting muscarinic antagonist aimed at improving the lung function of patients with COPD. Yupelri is an inhalation solution administered once daily through a standard jet nebulizer.
The most common adverse events associated with Yupelri are cough, nasopharyngitis, upper respiratory tract infection, headache, and back pain. Patients receiving other anticholinergic-containing drugs or OATP1B1 and OATP1B3 inhibitors should not receive Yupelri.
“Patients should also be alert for signs and symptoms of acute narrow-angle glaucoma [e.g., eye pain or discomfort, blurred vision, visual changes]. Patients should consult a healthcare professional immediately if any of these signs or symptoms develop,” the FDA said in the press release.
The expanded label for Yupelri can be found on the FDA website.
The Food and Drug Administration has approved Yupelri (revefenacin) for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD).
Revefenacin is a long-acting muscarinic antagonist aimed at improving the lung function of patients with COPD. Yupelri is an inhalation solution administered once daily through a standard jet nebulizer.
The most common adverse events associated with Yupelri are cough, nasopharyngitis, upper respiratory tract infection, headache, and back pain. Patients receiving other anticholinergic-containing drugs or OATP1B1 and OATP1B3 inhibitors should not receive Yupelri.
“Patients should also be alert for signs and symptoms of acute narrow-angle glaucoma [e.g., eye pain or discomfort, blurred vision, visual changes]. Patients should consult a healthcare professional immediately if any of these signs or symptoms develop,” the FDA said in the press release.
The expanded label for Yupelri can be found on the FDA website.
The Food and Drug Administration has approved Yupelri (revefenacin) for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD).
Revefenacin is a long-acting muscarinic antagonist aimed at improving the lung function of patients with COPD. Yupelri is an inhalation solution administered once daily through a standard jet nebulizer.
The most common adverse events associated with Yupelri are cough, nasopharyngitis, upper respiratory tract infection, headache, and back pain. Patients receiving other anticholinergic-containing drugs or OATP1B1 and OATP1B3 inhibitors should not receive Yupelri.
“Patients should also be alert for signs and symptoms of acute narrow-angle glaucoma [e.g., eye pain or discomfort, blurred vision, visual changes]. Patients should consult a healthcare professional immediately if any of these signs or symptoms develop,” the FDA said in the press release.
The expanded label for Yupelri can be found on the FDA website.
Pneumonia, COPD most common emergency care–sensitive conditions
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
REPORTING FROM ACEP18
Key clinical point: Emergency care–sensitive conditions (ECSCs) make up a significant proportion of ED visits.
Major finding: The most common ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), and asthma (7%).
Study details: A retrospective cohort study of more than 86.5 million ECSC-related ED visits.
Disclosures: Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.