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Asthma hospitalization in kids linked with doubled migraine incidence
when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.
Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.
“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.
Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.
Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.
The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.
Dr. Patel reported no relevant disclosures.
SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.
when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.
Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.
“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.
Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.
Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.
The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.
Dr. Patel reported no relevant disclosures.
SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.
when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.
Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.
“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.
Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.
Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.
The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.
Dr. Patel reported no relevant disclosures.
SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.
REPORTING FROM AHS 2019
Study: Cardiac biomarkers predicted CV events in CAP
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
FROM CHEST
Exposure to outdoor air pollutants linked to increased emphysema
Long-term exposure to ambient air pollutants was significantly associated with increases in emphysema and decreases in lung function, according to a diverse cohort study of six U.S. metropolitan areas.
“These associations in a community-based population demonstrate novel evidence that air pollution contributes to worsening lung health,” wrote Meng Wang, PhD, of the University of Washington, Seattle, and coauthors. The study was published in JAMA.
To determine whether exposure to outdoor air pollutants was associated with emphysema progression and change in lung function, the Multiethnic Study of Atherosclerosis (MESA) assessed 6,860 participants from six areas: Winston-Salem, N.C.; New York City; Baltimore; St. Paul, Minn.; Chicago; and Los Angeles. Percent emphysema was calculated based on all available CT scans; lung function was assessed via spirometry.
Spatiotemporal exposure models were developed for ozone, fine particulate matter less than 2.5 mcm in aerodynamic diameter, and oxides of nitrogen in each area based on Environmental Protection Agency measurements and the study’s cohort-specific monitoring. Annual mean concentrations of fine particulate matter and nitrogen decreased during follow-up, while ozone concentrations did not.
All participants underwent a cardiac CT scan at baseline, and 5,780 had at least one follow-up CT scan over a median period of 10 years. Ambient concentrations of ozone, fine particulate matter, nitrogen, and black carbon at baseline were significantly associated with greater increases in percent emphysema per 10 years, as were concentrations of zone and nitrogen during follow-up, reported Dr. Wang, formerly with the State University of New York at Buffalo.
Of the 3,636 participants who had at least one spirometric assessment, there was a mean decline in forced expiratory volume in 1 second (FEV1) of 309 mL (95% CI, 299-319 mL) and in forced vital capacity of 331 mL (95% CI, 317-345 mL) over 10 years. Ambient concentrations of ozone were significantly associated with a decline in FEV1, both at baseline and during follow-up.
The coauthors acknowledged their study’s limitations, including that general outdoor air pollution concentrations might not reflect individual exposure or concentrations indoors, where people spend most of their time. In addition, percent emphysema was only measured in the lower two-thirds of the lung, though they noted that “percent emphysema measured in the lower two-thirds of the lung correlates well with full-lung percent emphysema in this cohort and a cohort of smokers.”
This article was developed by the EPA and the University of Washington Center for Clean Air Research. MESA was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute, and supported by the National Institute of Environmental Health Sciences. The authors reported numerous conflicts of interest, including receiving grants and fees from the University of Washington, the EPA, the NIH, and various other pharmaceutical companies, foundations, and governmental entities.
SOURCE: Wang M et al. JAMA. 2019 Aug 13. doi: 10.1001/jama.2019.10255
Long-term exposure to ambient air pollutants was significantly associated with increases in emphysema and decreases in lung function, according to a diverse cohort study of six U.S. metropolitan areas.
“These associations in a community-based population demonstrate novel evidence that air pollution contributes to worsening lung health,” wrote Meng Wang, PhD, of the University of Washington, Seattle, and coauthors. The study was published in JAMA.
To determine whether exposure to outdoor air pollutants was associated with emphysema progression and change in lung function, the Multiethnic Study of Atherosclerosis (MESA) assessed 6,860 participants from six areas: Winston-Salem, N.C.; New York City; Baltimore; St. Paul, Minn.; Chicago; and Los Angeles. Percent emphysema was calculated based on all available CT scans; lung function was assessed via spirometry.
Spatiotemporal exposure models were developed for ozone, fine particulate matter less than 2.5 mcm in aerodynamic diameter, and oxides of nitrogen in each area based on Environmental Protection Agency measurements and the study’s cohort-specific monitoring. Annual mean concentrations of fine particulate matter and nitrogen decreased during follow-up, while ozone concentrations did not.
All participants underwent a cardiac CT scan at baseline, and 5,780 had at least one follow-up CT scan over a median period of 10 years. Ambient concentrations of ozone, fine particulate matter, nitrogen, and black carbon at baseline were significantly associated with greater increases in percent emphysema per 10 years, as were concentrations of zone and nitrogen during follow-up, reported Dr. Wang, formerly with the State University of New York at Buffalo.
Of the 3,636 participants who had at least one spirometric assessment, there was a mean decline in forced expiratory volume in 1 second (FEV1) of 309 mL (95% CI, 299-319 mL) and in forced vital capacity of 331 mL (95% CI, 317-345 mL) over 10 years. Ambient concentrations of ozone were significantly associated with a decline in FEV1, both at baseline and during follow-up.
The coauthors acknowledged their study’s limitations, including that general outdoor air pollution concentrations might not reflect individual exposure or concentrations indoors, where people spend most of their time. In addition, percent emphysema was only measured in the lower two-thirds of the lung, though they noted that “percent emphysema measured in the lower two-thirds of the lung correlates well with full-lung percent emphysema in this cohort and a cohort of smokers.”
This article was developed by the EPA and the University of Washington Center for Clean Air Research. MESA was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute, and supported by the National Institute of Environmental Health Sciences. The authors reported numerous conflicts of interest, including receiving grants and fees from the University of Washington, the EPA, the NIH, and various other pharmaceutical companies, foundations, and governmental entities.
SOURCE: Wang M et al. JAMA. 2019 Aug 13. doi: 10.1001/jama.2019.10255
Long-term exposure to ambient air pollutants was significantly associated with increases in emphysema and decreases in lung function, according to a diverse cohort study of six U.S. metropolitan areas.
“These associations in a community-based population demonstrate novel evidence that air pollution contributes to worsening lung health,” wrote Meng Wang, PhD, of the University of Washington, Seattle, and coauthors. The study was published in JAMA.
To determine whether exposure to outdoor air pollutants was associated with emphysema progression and change in lung function, the Multiethnic Study of Atherosclerosis (MESA) assessed 6,860 participants from six areas: Winston-Salem, N.C.; New York City; Baltimore; St. Paul, Minn.; Chicago; and Los Angeles. Percent emphysema was calculated based on all available CT scans; lung function was assessed via spirometry.
Spatiotemporal exposure models were developed for ozone, fine particulate matter less than 2.5 mcm in aerodynamic diameter, and oxides of nitrogen in each area based on Environmental Protection Agency measurements and the study’s cohort-specific monitoring. Annual mean concentrations of fine particulate matter and nitrogen decreased during follow-up, while ozone concentrations did not.
All participants underwent a cardiac CT scan at baseline, and 5,780 had at least one follow-up CT scan over a median period of 10 years. Ambient concentrations of ozone, fine particulate matter, nitrogen, and black carbon at baseline were significantly associated with greater increases in percent emphysema per 10 years, as were concentrations of zone and nitrogen during follow-up, reported Dr. Wang, formerly with the State University of New York at Buffalo.
Of the 3,636 participants who had at least one spirometric assessment, there was a mean decline in forced expiratory volume in 1 second (FEV1) of 309 mL (95% CI, 299-319 mL) and in forced vital capacity of 331 mL (95% CI, 317-345 mL) over 10 years. Ambient concentrations of ozone were significantly associated with a decline in FEV1, both at baseline and during follow-up.
The coauthors acknowledged their study’s limitations, including that general outdoor air pollution concentrations might not reflect individual exposure or concentrations indoors, where people spend most of their time. In addition, percent emphysema was only measured in the lower two-thirds of the lung, though they noted that “percent emphysema measured in the lower two-thirds of the lung correlates well with full-lung percent emphysema in this cohort and a cohort of smokers.”
This article was developed by the EPA and the University of Washington Center for Clean Air Research. MESA was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute, and supported by the National Institute of Environmental Health Sciences. The authors reported numerous conflicts of interest, including receiving grants and fees from the University of Washington, the EPA, the NIH, and various other pharmaceutical companies, foundations, and governmental entities.
SOURCE: Wang M et al. JAMA. 2019 Aug 13. doi: 10.1001/jama.2019.10255
FROM JAMA
Procalcitonin advocated to help rule out bacterial infections
SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.
It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.
There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.
Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.
Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).
Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.
Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).
“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.
Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).
As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.
Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).
The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.
It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.
There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.
Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.
Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).
Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.
Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).
“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.
Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).
As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.
Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).
The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.
It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.
There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.
Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.
Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).
Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.
Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).
“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.
Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).
As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.
Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).
The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
EXPERT ANALYSIS FROM PHM 2019
Vaping in 2019: Risk vs. reward
The prevalence and popularity of electronic cigarettes or “vaping” have grown dramatically over the last several years in the United States. Although new studies targeting these products are being done at increasing frequency, there remains a relative paucity of data regarding the long-term risks. Proponents argue that they can be used as a cessation tool for smokers, or failing that, a safer replacement for traditional cigarettes. Opponents make the case that the perception of safety could contribute to increased use in people who may have otherwise never smoked, leading to an overall increase in nicotine use and addiction. This is most readily seen in the adolescent population, where use has skyrocketed, leading to concerns about how electronic cigarettes are marketed to youth, as well as the ease of access.
Basics of vaping (devices)
In its most basic form, an electronic cigarette consists of a battery that powers a heating coil. This heating coil applies heat to a wick, which is soaked in liquid, “vape juice,” converting it into a vapor that is then directly inhaled. However, there can be many variations on this simple theme. Early generation products resembled traditional cigarettes in size and shape and were marketed as smoking cessation aids. Newer devices have abandoned this look and strategy. Preloaded cartridges have been replaced by large tanks that the user can fill with the liquid of their choosing. Multiple tanks can be purchased for a single device, enabling the user to have multiple flavors or various levels of nicotine dosing on hand for quick changing, depending on user preference or mood. Additionally, there are variable voltage settings, resulting in different styles of vapor and/or “throat hit” (the description of the desired burning vs smooth effect of the vapor on the oropharynx). This type of device invites experimentation. Multiple flavors can be used in isolation or mixed together at various temperatures. It no longer resembles classic cigarettes, and the flavor and experience are more prominently promoted. One can see that this device has more appeal to a “never smoker” than the original products, and there is concern that it is being marketed as such with some success (Dinakar C, et al. N Engl J Med. 2016;375[14]:1372).
E-liquid
Perhaps more important than the devices themselves is an understanding of the components of the liquid used to generate the inhaled aerosol.
Typically, four components are present:
• Propylene glycol
• Vegetable glycerin
• Flavoring
• Nicotine
The first two components are generally considered nontoxic, based on their use as food additives. However, inhalation is a novel route of entry and the long-term effects on the respiratory tract are unclear.
The third component, “flavorings,” is a catch-all term for the hundreds of different flavors and styles of e-liquids available today, ranging from menthol to fruit or candy and everything in between. It is difficult to account for all the potential effects of the numerous flavorings being used, especially when some are combined by the end user to various degrees.
Nicotine is present, specified in varying doses. However, vaping style, experience, and type of device used can dramatically affect how much is absorbed, making dosages difficult to predict. Additionally, labeled doses are prone to wide ranges of error (Schraufnagel DE, et al. Am J Respir Crit Care Med. 2014;190[6]:611).
What are the risks?
Cancer
A handful of known carcinogens can be found in inhaled vapor, including formaldehyde, acetaldehyde, acrolein, toluene, and nitrosamines. However, they are present in far lower concentrations than in traditional cigarettes (Goniewicz ML, et al. JAMA Netw Open. 2018;1[8]e185937). This leads to the natural assumption that vaping, while not benign, poses a much lower cancer risk when compared with smoking. Whether that is borne out in the long term remains to be seen.
Pulmonary function
The long-term effect on pulmonary function is not known. Small studies have shown no significant changes to spirometry after acute exposure to vapor. More data are needed in this area (Palazzolo DL. Frontiers Public Health. 2013;1[56]1-20).
Wound healing
An animal study has shown evidence of poor wound healing extrapolated from skin flap necrosis in rats. Exposure to vapor vs smoke yielded similar results, and both were worse than the sham arm (Troiano C, et al. JAMA Facial Plast Surg. 2019;21[1]:5). While it is difficult to know how to apply this clinically, it may be prudent to advise patients to abstain while in preparation for elective surgery.
Cardiovascular/stroke
Much of the cardiovascular toxicity from cigarette use is tied to the myriad of complex toxic particles produced in inhaled smoke, the vast majority of which are not present in e-cigarette vapor. While nicotine itself has known acute cardiovascular effects, including tachycardia and vasoconstriction, a tolerance to these effects occurs over time. Previous evaluations of nicotine replacement therapies and smokeless tobacco for their cardiovascular effects have had mixed results. But, there appears to be a trend toward minimal cardiovascular risk when using “cleaner” products, such as nicotine replacement therapy compared with smokeless tobacco (Benowitz NL, et al. Nature Rev Cardiol. 2017;14[8]:447). Whether this can be extrapolated to electronic cigarette use is unknown but is encouraging.
Alternative toxicity
In addition to the above risks that are in comparison to traditional smoking, vaping also introduces novel toxicities. There are case reports of lipoid pneumonia, ARDS, hypersensitivity pneumonitis, eosinophilic pneumonia, and diffuse alveola hemorrhage. Burns from malfunctioning devices must also be considered, as there is a wide array of products available, at differing levels of build quality.
Toxic oral ingestion of nicotine, especially by children, has led to increased calls to poison centers. For a small child, this can be fatal. Regulation of labels and containers could curtail this issue. But, public education regarding the toxicity of these substances when ingested in large quantities is also important. If there is a lack of understanding about this danger, then typical safeguards are easily overlooked by individual users.
Are there benefits?
Smoking cessation
Compared with other products, such as nicotine patches, gum, and pharmaceutical methods, e-cigarettes most closely mimic the actual experience of smoking. For some, the habit and ritual of smoking is as much a part of the addiction as nicotine. Vaping has the potential to help alleviate this difficult aspect of cessation. Data involving early generation products failed to show a significant advantage. Newer devices that are more pleasurable to use and offer more efficient nicotine delivery may be more effective. Indeed, a recent study in the New England Journal of Medicine from this year demonstrated improved smoking cessation compared with traditional methods, using second generation vape devices (Hajek P, et al. N Engl J Med. 2019;380[7]629). It will be interesting to see if this can be repeatable going forward and if protocols can be established to maximize effectiveness.
As outlined above, it is difficult to make definitive conclusions or recommendations regarding electronic cigarette use at the present time. The risk of cancer and cardiopulmonary disease is likely to be significantly lower but not eliminated. Use as a smoking cessation aid is starting to show promise. Even without cessation, ongoing vaping is likely to be safer than ongoing smoking. Two caveats to this remain: some patients, in an effort to quit smoking, may take up vaping but eventually become “dual users.” This scenario has been associated with higher toxic exposure and possibly worse outcomes. The second caveat is that while there is promise to using this as a cessation tool, it should not yet replace other more well-studied, first-line agents in this regard. It should, perhaps, target patients who are motivated to quit but have failed more traditional methods. Finally, there continues to be concern that vaping could appeal to never smokers, given its perceived safety profile and ease of use in public places. This could lead to an overall increase in nicotine addiction, which could be a significant step backwards.
Dr. Clark is Assistant Professor, Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, Texas.
The prevalence and popularity of electronic cigarettes or “vaping” have grown dramatically over the last several years in the United States. Although new studies targeting these products are being done at increasing frequency, there remains a relative paucity of data regarding the long-term risks. Proponents argue that they can be used as a cessation tool for smokers, or failing that, a safer replacement for traditional cigarettes. Opponents make the case that the perception of safety could contribute to increased use in people who may have otherwise never smoked, leading to an overall increase in nicotine use and addiction. This is most readily seen in the adolescent population, where use has skyrocketed, leading to concerns about how electronic cigarettes are marketed to youth, as well as the ease of access.
Basics of vaping (devices)
In its most basic form, an electronic cigarette consists of a battery that powers a heating coil. This heating coil applies heat to a wick, which is soaked in liquid, “vape juice,” converting it into a vapor that is then directly inhaled. However, there can be many variations on this simple theme. Early generation products resembled traditional cigarettes in size and shape and were marketed as smoking cessation aids. Newer devices have abandoned this look and strategy. Preloaded cartridges have been replaced by large tanks that the user can fill with the liquid of their choosing. Multiple tanks can be purchased for a single device, enabling the user to have multiple flavors or various levels of nicotine dosing on hand for quick changing, depending on user preference or mood. Additionally, there are variable voltage settings, resulting in different styles of vapor and/or “throat hit” (the description of the desired burning vs smooth effect of the vapor on the oropharynx). This type of device invites experimentation. Multiple flavors can be used in isolation or mixed together at various temperatures. It no longer resembles classic cigarettes, and the flavor and experience are more prominently promoted. One can see that this device has more appeal to a “never smoker” than the original products, and there is concern that it is being marketed as such with some success (Dinakar C, et al. N Engl J Med. 2016;375[14]:1372).
E-liquid
Perhaps more important than the devices themselves is an understanding of the components of the liquid used to generate the inhaled aerosol.
Typically, four components are present:
• Propylene glycol
• Vegetable glycerin
• Flavoring
• Nicotine
The first two components are generally considered nontoxic, based on their use as food additives. However, inhalation is a novel route of entry and the long-term effects on the respiratory tract are unclear.
The third component, “flavorings,” is a catch-all term for the hundreds of different flavors and styles of e-liquids available today, ranging from menthol to fruit or candy and everything in between. It is difficult to account for all the potential effects of the numerous flavorings being used, especially when some are combined by the end user to various degrees.
Nicotine is present, specified in varying doses. However, vaping style, experience, and type of device used can dramatically affect how much is absorbed, making dosages difficult to predict. Additionally, labeled doses are prone to wide ranges of error (Schraufnagel DE, et al. Am J Respir Crit Care Med. 2014;190[6]:611).
What are the risks?
Cancer
A handful of known carcinogens can be found in inhaled vapor, including formaldehyde, acetaldehyde, acrolein, toluene, and nitrosamines. However, they are present in far lower concentrations than in traditional cigarettes (Goniewicz ML, et al. JAMA Netw Open. 2018;1[8]e185937). This leads to the natural assumption that vaping, while not benign, poses a much lower cancer risk when compared with smoking. Whether that is borne out in the long term remains to be seen.
Pulmonary function
The long-term effect on pulmonary function is not known. Small studies have shown no significant changes to spirometry after acute exposure to vapor. More data are needed in this area (Palazzolo DL. Frontiers Public Health. 2013;1[56]1-20).
Wound healing
An animal study has shown evidence of poor wound healing extrapolated from skin flap necrosis in rats. Exposure to vapor vs smoke yielded similar results, and both were worse than the sham arm (Troiano C, et al. JAMA Facial Plast Surg. 2019;21[1]:5). While it is difficult to know how to apply this clinically, it may be prudent to advise patients to abstain while in preparation for elective surgery.
Cardiovascular/stroke
Much of the cardiovascular toxicity from cigarette use is tied to the myriad of complex toxic particles produced in inhaled smoke, the vast majority of which are not present in e-cigarette vapor. While nicotine itself has known acute cardiovascular effects, including tachycardia and vasoconstriction, a tolerance to these effects occurs over time. Previous evaluations of nicotine replacement therapies and smokeless tobacco for their cardiovascular effects have had mixed results. But, there appears to be a trend toward minimal cardiovascular risk when using “cleaner” products, such as nicotine replacement therapy compared with smokeless tobacco (Benowitz NL, et al. Nature Rev Cardiol. 2017;14[8]:447). Whether this can be extrapolated to electronic cigarette use is unknown but is encouraging.
Alternative toxicity
In addition to the above risks that are in comparison to traditional smoking, vaping also introduces novel toxicities. There are case reports of lipoid pneumonia, ARDS, hypersensitivity pneumonitis, eosinophilic pneumonia, and diffuse alveola hemorrhage. Burns from malfunctioning devices must also be considered, as there is a wide array of products available, at differing levels of build quality.
Toxic oral ingestion of nicotine, especially by children, has led to increased calls to poison centers. For a small child, this can be fatal. Regulation of labels and containers could curtail this issue. But, public education regarding the toxicity of these substances when ingested in large quantities is also important. If there is a lack of understanding about this danger, then typical safeguards are easily overlooked by individual users.
Are there benefits?
Smoking cessation
Compared with other products, such as nicotine patches, gum, and pharmaceutical methods, e-cigarettes most closely mimic the actual experience of smoking. For some, the habit and ritual of smoking is as much a part of the addiction as nicotine. Vaping has the potential to help alleviate this difficult aspect of cessation. Data involving early generation products failed to show a significant advantage. Newer devices that are more pleasurable to use and offer more efficient nicotine delivery may be more effective. Indeed, a recent study in the New England Journal of Medicine from this year demonstrated improved smoking cessation compared with traditional methods, using second generation vape devices (Hajek P, et al. N Engl J Med. 2019;380[7]629). It will be interesting to see if this can be repeatable going forward and if protocols can be established to maximize effectiveness.
As outlined above, it is difficult to make definitive conclusions or recommendations regarding electronic cigarette use at the present time. The risk of cancer and cardiopulmonary disease is likely to be significantly lower but not eliminated. Use as a smoking cessation aid is starting to show promise. Even without cessation, ongoing vaping is likely to be safer than ongoing smoking. Two caveats to this remain: some patients, in an effort to quit smoking, may take up vaping but eventually become “dual users.” This scenario has been associated with higher toxic exposure and possibly worse outcomes. The second caveat is that while there is promise to using this as a cessation tool, it should not yet replace other more well-studied, first-line agents in this regard. It should, perhaps, target patients who are motivated to quit but have failed more traditional methods. Finally, there continues to be concern that vaping could appeal to never smokers, given its perceived safety profile and ease of use in public places. This could lead to an overall increase in nicotine addiction, which could be a significant step backwards.
Dr. Clark is Assistant Professor, Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, Texas.
The prevalence and popularity of electronic cigarettes or “vaping” have grown dramatically over the last several years in the United States. Although new studies targeting these products are being done at increasing frequency, there remains a relative paucity of data regarding the long-term risks. Proponents argue that they can be used as a cessation tool for smokers, or failing that, a safer replacement for traditional cigarettes. Opponents make the case that the perception of safety could contribute to increased use in people who may have otherwise never smoked, leading to an overall increase in nicotine use and addiction. This is most readily seen in the adolescent population, where use has skyrocketed, leading to concerns about how electronic cigarettes are marketed to youth, as well as the ease of access.
Basics of vaping (devices)
In its most basic form, an electronic cigarette consists of a battery that powers a heating coil. This heating coil applies heat to a wick, which is soaked in liquid, “vape juice,” converting it into a vapor that is then directly inhaled. However, there can be many variations on this simple theme. Early generation products resembled traditional cigarettes in size and shape and were marketed as smoking cessation aids. Newer devices have abandoned this look and strategy. Preloaded cartridges have been replaced by large tanks that the user can fill with the liquid of their choosing. Multiple tanks can be purchased for a single device, enabling the user to have multiple flavors or various levels of nicotine dosing on hand for quick changing, depending on user preference or mood. Additionally, there are variable voltage settings, resulting in different styles of vapor and/or “throat hit” (the description of the desired burning vs smooth effect of the vapor on the oropharynx). This type of device invites experimentation. Multiple flavors can be used in isolation or mixed together at various temperatures. It no longer resembles classic cigarettes, and the flavor and experience are more prominently promoted. One can see that this device has more appeal to a “never smoker” than the original products, and there is concern that it is being marketed as such with some success (Dinakar C, et al. N Engl J Med. 2016;375[14]:1372).
E-liquid
Perhaps more important than the devices themselves is an understanding of the components of the liquid used to generate the inhaled aerosol.
Typically, four components are present:
• Propylene glycol
• Vegetable glycerin
• Flavoring
• Nicotine
The first two components are generally considered nontoxic, based on their use as food additives. However, inhalation is a novel route of entry and the long-term effects on the respiratory tract are unclear.
The third component, “flavorings,” is a catch-all term for the hundreds of different flavors and styles of e-liquids available today, ranging from menthol to fruit or candy and everything in between. It is difficult to account for all the potential effects of the numerous flavorings being used, especially when some are combined by the end user to various degrees.
Nicotine is present, specified in varying doses. However, vaping style, experience, and type of device used can dramatically affect how much is absorbed, making dosages difficult to predict. Additionally, labeled doses are prone to wide ranges of error (Schraufnagel DE, et al. Am J Respir Crit Care Med. 2014;190[6]:611).
What are the risks?
Cancer
A handful of known carcinogens can be found in inhaled vapor, including formaldehyde, acetaldehyde, acrolein, toluene, and nitrosamines. However, they are present in far lower concentrations than in traditional cigarettes (Goniewicz ML, et al. JAMA Netw Open. 2018;1[8]e185937). This leads to the natural assumption that vaping, while not benign, poses a much lower cancer risk when compared with smoking. Whether that is borne out in the long term remains to be seen.
Pulmonary function
The long-term effect on pulmonary function is not known. Small studies have shown no significant changes to spirometry after acute exposure to vapor. More data are needed in this area (Palazzolo DL. Frontiers Public Health. 2013;1[56]1-20).
Wound healing
An animal study has shown evidence of poor wound healing extrapolated from skin flap necrosis in rats. Exposure to vapor vs smoke yielded similar results, and both were worse than the sham arm (Troiano C, et al. JAMA Facial Plast Surg. 2019;21[1]:5). While it is difficult to know how to apply this clinically, it may be prudent to advise patients to abstain while in preparation for elective surgery.
Cardiovascular/stroke
Much of the cardiovascular toxicity from cigarette use is tied to the myriad of complex toxic particles produced in inhaled smoke, the vast majority of which are not present in e-cigarette vapor. While nicotine itself has known acute cardiovascular effects, including tachycardia and vasoconstriction, a tolerance to these effects occurs over time. Previous evaluations of nicotine replacement therapies and smokeless tobacco for their cardiovascular effects have had mixed results. But, there appears to be a trend toward minimal cardiovascular risk when using “cleaner” products, such as nicotine replacement therapy compared with smokeless tobacco (Benowitz NL, et al. Nature Rev Cardiol. 2017;14[8]:447). Whether this can be extrapolated to electronic cigarette use is unknown but is encouraging.
Alternative toxicity
In addition to the above risks that are in comparison to traditional smoking, vaping also introduces novel toxicities. There are case reports of lipoid pneumonia, ARDS, hypersensitivity pneumonitis, eosinophilic pneumonia, and diffuse alveola hemorrhage. Burns from malfunctioning devices must also be considered, as there is a wide array of products available, at differing levels of build quality.
Toxic oral ingestion of nicotine, especially by children, has led to increased calls to poison centers. For a small child, this can be fatal. Regulation of labels and containers could curtail this issue. But, public education regarding the toxicity of these substances when ingested in large quantities is also important. If there is a lack of understanding about this danger, then typical safeguards are easily overlooked by individual users.
Are there benefits?
Smoking cessation
Compared with other products, such as nicotine patches, gum, and pharmaceutical methods, e-cigarettes most closely mimic the actual experience of smoking. For some, the habit and ritual of smoking is as much a part of the addiction as nicotine. Vaping has the potential to help alleviate this difficult aspect of cessation. Data involving early generation products failed to show a significant advantage. Newer devices that are more pleasurable to use and offer more efficient nicotine delivery may be more effective. Indeed, a recent study in the New England Journal of Medicine from this year demonstrated improved smoking cessation compared with traditional methods, using second generation vape devices (Hajek P, et al. N Engl J Med. 2019;380[7]629). It will be interesting to see if this can be repeatable going forward and if protocols can be established to maximize effectiveness.
As outlined above, it is difficult to make definitive conclusions or recommendations regarding electronic cigarette use at the present time. The risk of cancer and cardiopulmonary disease is likely to be significantly lower but not eliminated. Use as a smoking cessation aid is starting to show promise. Even without cessation, ongoing vaping is likely to be safer than ongoing smoking. Two caveats to this remain: some patients, in an effort to quit smoking, may take up vaping but eventually become “dual users.” This scenario has been associated with higher toxic exposure and possibly worse outcomes. The second caveat is that while there is promise to using this as a cessation tool, it should not yet replace other more well-studied, first-line agents in this regard. It should, perhaps, target patients who are motivated to quit but have failed more traditional methods. Finally, there continues to be concern that vaping could appeal to never smokers, given its perceived safety profile and ease of use in public places. This could lead to an overall increase in nicotine addiction, which could be a significant step backwards.
Dr. Clark is Assistant Professor, Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, Texas.
Sepsis survivors’ persistent immunosuppression raises mortality risk
readmission after discharge, and mortality, according to a study published in JAMA Network Open.
“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”
Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.
Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).
From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.
“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.
This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.
SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.
readmission after discharge, and mortality, according to a study published in JAMA Network Open.
“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”
Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.
Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).
From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.
“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.
This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.
SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.
readmission after discharge, and mortality, according to a study published in JAMA Network Open.
“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”
Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.
Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).
From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.
“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.
This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.
SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.
FROM JAMA NETWORK OPEN
Key clinical point: Markers of inflammation and immunosuppression persist in over two-thirds of patients hospitalized for sepsis, which could explain worsened outcomes and mortality up to 1 year after hospitalization.
Major finding: Patients with signs of hyperinflammation and immunosuppression had significantly increased mortality after 1 year and were significantly more likely to be readmitted or die because of cardiovascular disease or cancer.
Study details: A prospective cohort study of 483 patients who were hospitalized because of sepsis at 12 different centers between January 2012 and May 2017.
Disclosures: This study was funded by grants from National Institutes of Health and resources from the Veterans Affairs Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.
Source: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.
mRNA technology for respiratory vaccines impresses
LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.
“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.
Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.
The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.
Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.
“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.
In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).
“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.
The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.
There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.
The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.
In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.
The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.
The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”
Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.
“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.
She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.
LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.
“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.
Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.
The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.
Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.
“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.
In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).
“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.
The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.
There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.
The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.
In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.
The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.
The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”
Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.
“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.
She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.
LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.
“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.
Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.
The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.
Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.
“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.
In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).
“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.
The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.
There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.
The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.
In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.
The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.
The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”
Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.
“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.
She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.
REPORTING FROM ESPID 2019
Patient and family education of asthma management is critical
ORLANDO – according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”
Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.
“We review their inhaler technique every time they come in,” she added.
According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.
“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.
Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.
To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.
Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.
The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”
When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.
“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.
Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.
ORLANDO – according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”
Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.
“We review their inhaler technique every time they come in,” she added.
According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.
“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.
Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.
To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.
Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.
The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”
When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.
“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.
Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.
ORLANDO – according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”
Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.
“We review their inhaler technique every time they come in,” she added.
According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.
“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.
Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.
To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.
Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.
The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”
When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.
“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.
Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM CARPS 2019
COPD adds complexity to shared decision making for LDCT lung cancer screening
research suggests.
Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).
Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.
Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.
In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.
At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.
“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.
The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).
“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”
They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.
Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.
The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.
SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.
research suggests.
Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).
Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.
Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.
In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.
At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.
“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.
The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).
“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”
They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.
Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.
The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.
SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.
research suggests.
Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).
Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.
Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.
In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.
At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.
“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.
The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).
“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”
They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.
Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.
The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.
SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.
FROM CHEST
Dispatch from HM19: COPD updates
Session presenter
Cathy Grossman MD, FCCP, CHSE
Session title
COPD Updates 2019
Session summary
Chronic obstructive pulmonary disease (COPD) is the third most common cause of death in the United States and accounts for close to 730,000 admissions and 120,000 deaths per year.1 That correlates to one death every 4 minutes. By 2020, the adjusted cost of COPD in the United States was projected to be approximately $50 billion.2
Every COPD exacerbation is associated with economic, social, and mortality burdens. The probability of survival decreases to 20% by the end of 5 years in patients with frequent readmissions, compared with patients with no acute exacerbations of COPD.3 The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recently released its 2019 report and gave fresh guidance on medication changes to consider in patients who have had a COPD exacerbation.
At HM19, Cathy Grossman, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at Virginia Commonwealth University, Richmond, discussed the updates. She explained that most of the patients who are treated by hospitalists are GOLD group C or group D, and stressed the importance of involving the pulmonology team in the care of these patients.
Dr. Grossman explained that GOLD 2019 recommended using eosinophil counts to predict the effect of inhaled corticosteroids (ICS), added to regular maintenance bronchodilator treatment, in preventing future exacerbations. These effects are observed to be incrementally increasing at higher eosinophil counts. For patients who are taking a long-acting beta2-agonist or muscarinic antagonist (LABA or LAMA), and have a high eosinophil count (at least 300 cells/mcL, or at least 100 cells/mcL plus a history of several exacerbations), one could consider adding an ICS.4 For patients who don’t fulfill these criteria, one could try a LABA plus a LAMA. However, one has to be cautious as some of these patients get intravenous dexamethasone by EMS and admission labs may not show eosinophils.
A caveat to using ICS is that, in some of these of the patients, ICS may lead to bacterial overgrowth and therefore more pneumonias, and that may be contributing to frequent admissions of these patients. In such patients, discontinuation might be a viable option. The guidelines recommend starting GOLD group C and D patients with LAMA or LAMA/LABA combination inhalers, and ICS if they have high eosinophil counts. If patients are already on triple therapy, one could add roflumilast5 or a macrolide.
The effectiveness of noninvasive positive-pressure ventilation (NIV) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure remains unclear, although there is some data to support the use of home NIV in patients with COPD and obstructive sleep apnea, both with and without hypercapnia. Dr. Grossman mentioned that there are still many unanswered questions, like identifying the right patient, right time, and right settings, and more studies are underway.
Dr. Grossman concluded that bread-and-butter topics like smoking cessation counseling, inhaler instruction, and referral to pulmonary rehab are still the most important tools to decrease COPD exacerbations.
Dr. Jonnalagadda is a physician advisor, and Dr. Medarametla is medical director, of hospital medicine at Baystate Medical Center in Springfield, Mass.
References
1. Guarascio AJ et al. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. Clinicoecon Outcomes Res. 2013 Jun 17;5:235-45.
2. Morbidity & Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Disease. National Institutes of Health and National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/files/docs/research/2012_ChartBook_508.pdf.
3. Soler-Cataluña JJ et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease; Thorax. 2005;60:925-31.
4. Cheng SL. Blood eosinophils and inhaled corticosteroids in patients with COPD: Systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2018 Sept 6;13:2775-84.
5. FJ Martinez et al. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): A multicenter, randomized, controlled trial. Lancet. 2015;385(9971):857-66.
Session presenter
Cathy Grossman MD, FCCP, CHSE
Session title
COPD Updates 2019
Session summary
Chronic obstructive pulmonary disease (COPD) is the third most common cause of death in the United States and accounts for close to 730,000 admissions and 120,000 deaths per year.1 That correlates to one death every 4 minutes. By 2020, the adjusted cost of COPD in the United States was projected to be approximately $50 billion.2
Every COPD exacerbation is associated with economic, social, and mortality burdens. The probability of survival decreases to 20% by the end of 5 years in patients with frequent readmissions, compared with patients with no acute exacerbations of COPD.3 The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recently released its 2019 report and gave fresh guidance on medication changes to consider in patients who have had a COPD exacerbation.
At HM19, Cathy Grossman, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at Virginia Commonwealth University, Richmond, discussed the updates. She explained that most of the patients who are treated by hospitalists are GOLD group C or group D, and stressed the importance of involving the pulmonology team in the care of these patients.
Dr. Grossman explained that GOLD 2019 recommended using eosinophil counts to predict the effect of inhaled corticosteroids (ICS), added to regular maintenance bronchodilator treatment, in preventing future exacerbations. These effects are observed to be incrementally increasing at higher eosinophil counts. For patients who are taking a long-acting beta2-agonist or muscarinic antagonist (LABA or LAMA), and have a high eosinophil count (at least 300 cells/mcL, or at least 100 cells/mcL plus a history of several exacerbations), one could consider adding an ICS.4 For patients who don’t fulfill these criteria, one could try a LABA plus a LAMA. However, one has to be cautious as some of these patients get intravenous dexamethasone by EMS and admission labs may not show eosinophils.
A caveat to using ICS is that, in some of these of the patients, ICS may lead to bacterial overgrowth and therefore more pneumonias, and that may be contributing to frequent admissions of these patients. In such patients, discontinuation might be a viable option. The guidelines recommend starting GOLD group C and D patients with LAMA or LAMA/LABA combination inhalers, and ICS if they have high eosinophil counts. If patients are already on triple therapy, one could add roflumilast5 or a macrolide.
The effectiveness of noninvasive positive-pressure ventilation (NIV) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure remains unclear, although there is some data to support the use of home NIV in patients with COPD and obstructive sleep apnea, both with and without hypercapnia. Dr. Grossman mentioned that there are still many unanswered questions, like identifying the right patient, right time, and right settings, and more studies are underway.
Dr. Grossman concluded that bread-and-butter topics like smoking cessation counseling, inhaler instruction, and referral to pulmonary rehab are still the most important tools to decrease COPD exacerbations.
Dr. Jonnalagadda is a physician advisor, and Dr. Medarametla is medical director, of hospital medicine at Baystate Medical Center in Springfield, Mass.
References
1. Guarascio AJ et al. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. Clinicoecon Outcomes Res. 2013 Jun 17;5:235-45.
2. Morbidity & Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Disease. National Institutes of Health and National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/files/docs/research/2012_ChartBook_508.pdf.
3. Soler-Cataluña JJ et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease; Thorax. 2005;60:925-31.
4. Cheng SL. Blood eosinophils and inhaled corticosteroids in patients with COPD: Systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2018 Sept 6;13:2775-84.
5. FJ Martinez et al. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): A multicenter, randomized, controlled trial. Lancet. 2015;385(9971):857-66.
Session presenter
Cathy Grossman MD, FCCP, CHSE
Session title
COPD Updates 2019
Session summary
Chronic obstructive pulmonary disease (COPD) is the third most common cause of death in the United States and accounts for close to 730,000 admissions and 120,000 deaths per year.1 That correlates to one death every 4 minutes. By 2020, the adjusted cost of COPD in the United States was projected to be approximately $50 billion.2
Every COPD exacerbation is associated with economic, social, and mortality burdens. The probability of survival decreases to 20% by the end of 5 years in patients with frequent readmissions, compared with patients with no acute exacerbations of COPD.3 The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recently released its 2019 report and gave fresh guidance on medication changes to consider in patients who have had a COPD exacerbation.
At HM19, Cathy Grossman, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at Virginia Commonwealth University, Richmond, discussed the updates. She explained that most of the patients who are treated by hospitalists are GOLD group C or group D, and stressed the importance of involving the pulmonology team in the care of these patients.
Dr. Grossman explained that GOLD 2019 recommended using eosinophil counts to predict the effect of inhaled corticosteroids (ICS), added to regular maintenance bronchodilator treatment, in preventing future exacerbations. These effects are observed to be incrementally increasing at higher eosinophil counts. For patients who are taking a long-acting beta2-agonist or muscarinic antagonist (LABA or LAMA), and have a high eosinophil count (at least 300 cells/mcL, or at least 100 cells/mcL plus a history of several exacerbations), one could consider adding an ICS.4 For patients who don’t fulfill these criteria, one could try a LABA plus a LAMA. However, one has to be cautious as some of these patients get intravenous dexamethasone by EMS and admission labs may not show eosinophils.
A caveat to using ICS is that, in some of these of the patients, ICS may lead to bacterial overgrowth and therefore more pneumonias, and that may be contributing to frequent admissions of these patients. In such patients, discontinuation might be a viable option. The guidelines recommend starting GOLD group C and D patients with LAMA or LAMA/LABA combination inhalers, and ICS if they have high eosinophil counts. If patients are already on triple therapy, one could add roflumilast5 or a macrolide.
The effectiveness of noninvasive positive-pressure ventilation (NIV) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure remains unclear, although there is some data to support the use of home NIV in patients with COPD and obstructive sleep apnea, both with and without hypercapnia. Dr. Grossman mentioned that there are still many unanswered questions, like identifying the right patient, right time, and right settings, and more studies are underway.
Dr. Grossman concluded that bread-and-butter topics like smoking cessation counseling, inhaler instruction, and referral to pulmonary rehab are still the most important tools to decrease COPD exacerbations.
Dr. Jonnalagadda is a physician advisor, and Dr. Medarametla is medical director, of hospital medicine at Baystate Medical Center in Springfield, Mass.
References
1. Guarascio AJ et al. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. Clinicoecon Outcomes Res. 2013 Jun 17;5:235-45.
2. Morbidity & Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Disease. National Institutes of Health and National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/files/docs/research/2012_ChartBook_508.pdf.
3. Soler-Cataluña JJ et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease; Thorax. 2005;60:925-31.
4. Cheng SL. Blood eosinophils and inhaled corticosteroids in patients with COPD: Systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2018 Sept 6;13:2775-84.
5. FJ Martinez et al. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): A multicenter, randomized, controlled trial. Lancet. 2015;385(9971):857-66.