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COPD rates reflect current smoking prevalence
, according to a Centers for Disease Control and Prevention analysis of respondents to a behavioral risk factor survey.
“Population-based strategies for smoking prevention and control have the potential to decrease the prevalence of COPD in the United States,” wrote Anne G. Wheaton, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and coauthors. The study was published in the Morbidity and Mortality Weekly Report.
Dr. Wheaton and her fellow researchers analyzed data from 418,378 adult respondents to the 2017 Behavioral Risk Factor Surveillance System survey. Responses came from all 50 states and Washington, D.C.; respondents who had smoked less than 100 lifetime cigarettes were categorized as “never smoked,” while those who had smoked at least 100 cigarettes but no longer smoked were categorized as “former smokers.” Anyone who had smoked at least 100 cigarettes and currently smoked was categorized as a “current smoker.”
The age-adjusted prevalence of COPD among U.S. adults was 6.2% (95% confidence interval, 6.0%-6.3%) in 2017. Current cigarette smokers had a prevalence of 15.2% (95% CI, 14.7%-15.7%); this dipped to 7.6% (95% CI, 7.3%-8.0%) among former smokers and 2.8% (95% CI, 2.7%-2.9%) among adults who had never smoked. Patterns were visible within states: Current smokers had a state-level prevalence of COPD that was strongly correlated with state-level current smoking prevalence (Pearson correlation coefficient, 0.69; P less than .001). State-level COPD prevalence among former smokers (Pearson correlation coefficient, 0.71; P less than .001) and those who never smoked (Pearson correlation coefficient, 0.64; P less than .001) were also strongly correlated with the current smoking prevalence, indicating secondhand smoke as a risk factor for COPD.
The coauthors acknowledged the study’s limitations, including relying on self-reporting for both COPD and smoking status. They also noted that there was no way to measure exposure to secondhand smoke, other indoor or outdoor air pollutants, or respiratory infection history, “all of which might contribute to COPD risk.”
No conflicts of interest were reported.
SOURCE: Wheaton AG et al. MMWR Morb Mortal Wkly Rep. 2019 Jun 21;68(24):533-8.
, according to a Centers for Disease Control and Prevention analysis of respondents to a behavioral risk factor survey.
“Population-based strategies for smoking prevention and control have the potential to decrease the prevalence of COPD in the United States,” wrote Anne G. Wheaton, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and coauthors. The study was published in the Morbidity and Mortality Weekly Report.
Dr. Wheaton and her fellow researchers analyzed data from 418,378 adult respondents to the 2017 Behavioral Risk Factor Surveillance System survey. Responses came from all 50 states and Washington, D.C.; respondents who had smoked less than 100 lifetime cigarettes were categorized as “never smoked,” while those who had smoked at least 100 cigarettes but no longer smoked were categorized as “former smokers.” Anyone who had smoked at least 100 cigarettes and currently smoked was categorized as a “current smoker.”
The age-adjusted prevalence of COPD among U.S. adults was 6.2% (95% confidence interval, 6.0%-6.3%) in 2017. Current cigarette smokers had a prevalence of 15.2% (95% CI, 14.7%-15.7%); this dipped to 7.6% (95% CI, 7.3%-8.0%) among former smokers and 2.8% (95% CI, 2.7%-2.9%) among adults who had never smoked. Patterns were visible within states: Current smokers had a state-level prevalence of COPD that was strongly correlated with state-level current smoking prevalence (Pearson correlation coefficient, 0.69; P less than .001). State-level COPD prevalence among former smokers (Pearson correlation coefficient, 0.71; P less than .001) and those who never smoked (Pearson correlation coefficient, 0.64; P less than .001) were also strongly correlated with the current smoking prevalence, indicating secondhand smoke as a risk factor for COPD.
The coauthors acknowledged the study’s limitations, including relying on self-reporting for both COPD and smoking status. They also noted that there was no way to measure exposure to secondhand smoke, other indoor or outdoor air pollutants, or respiratory infection history, “all of which might contribute to COPD risk.”
No conflicts of interest were reported.
SOURCE: Wheaton AG et al. MMWR Morb Mortal Wkly Rep. 2019 Jun 21;68(24):533-8.
, according to a Centers for Disease Control and Prevention analysis of respondents to a behavioral risk factor survey.
“Population-based strategies for smoking prevention and control have the potential to decrease the prevalence of COPD in the United States,” wrote Anne G. Wheaton, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and coauthors. The study was published in the Morbidity and Mortality Weekly Report.
Dr. Wheaton and her fellow researchers analyzed data from 418,378 adult respondents to the 2017 Behavioral Risk Factor Surveillance System survey. Responses came from all 50 states and Washington, D.C.; respondents who had smoked less than 100 lifetime cigarettes were categorized as “never smoked,” while those who had smoked at least 100 cigarettes but no longer smoked were categorized as “former smokers.” Anyone who had smoked at least 100 cigarettes and currently smoked was categorized as a “current smoker.”
The age-adjusted prevalence of COPD among U.S. adults was 6.2% (95% confidence interval, 6.0%-6.3%) in 2017. Current cigarette smokers had a prevalence of 15.2% (95% CI, 14.7%-15.7%); this dipped to 7.6% (95% CI, 7.3%-8.0%) among former smokers and 2.8% (95% CI, 2.7%-2.9%) among adults who had never smoked. Patterns were visible within states: Current smokers had a state-level prevalence of COPD that was strongly correlated with state-level current smoking prevalence (Pearson correlation coefficient, 0.69; P less than .001). State-level COPD prevalence among former smokers (Pearson correlation coefficient, 0.71; P less than .001) and those who never smoked (Pearson correlation coefficient, 0.64; P less than .001) were also strongly correlated with the current smoking prevalence, indicating secondhand smoke as a risk factor for COPD.
The coauthors acknowledged the study’s limitations, including relying on self-reporting for both COPD and smoking status. They also noted that there was no way to measure exposure to secondhand smoke, other indoor or outdoor air pollutants, or respiratory infection history, “all of which might contribute to COPD risk.”
No conflicts of interest were reported.
SOURCE: Wheaton AG et al. MMWR Morb Mortal Wkly Rep. 2019 Jun 21;68(24):533-8.
FROM MMWR
Vaping among teens increased significantly from 2017 to 2018
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
according to data from national cross-sectional surveys.
The prevalence of vaping in the past 30 days rose from 11% to 16% in the United States and from 8% to 14.6% in Canada, while use in England showed an nonsignificant increase of 8.7% to 8.9%, David Hammond, PhD, of the University of Waterloo (Canada) and associates said in the BMJ.
Embedded in those U.S. and Canadian increases is the recent evolution of the vaping market brought about by “the growth of JUUL e-cigarettes and similar products [that use] benzoic acid and nicotine salt technology to deliver higher concentrations of nicotine than conventional e-cigarettes,” they explained.
In England, the JUUL system is limited to less than half the nicotine concentration, at 20 mg/mL, compared with more than 50 mg/mL in the United States and Canada, and it was not available at all types of retail outlets at the time of the surveys. That situation changed in March 2019, when the company expanded to convenience stores, the investigators noted.
In the United States, JUUL was the second-most popular product among past–30-day vapers who had a usual brand in 2017, with 9% reporting use. In 2018, JUUL was the most popular brand and use was up to 28%. In Canada, the brand was not among the top five in 2017, but was third in 2018 at 10% in those who reported vaping in the past 30 days. The leading Canadian brand in 2018 was Smok, which released a nicotine-salt version in March of 2018, Dr. Hammond and associates reported.
“Before 2018, there was relatively little evidence of regular vaping among adolescents that might be indicative of nicotine addiction; however, the emergence of JUUL and nicotine salt–based products might signal a change,” they wrote.
The International Tobacco Control Policy Evaluation Project’s Youth Tobacco and Vaping Survey was conducted online in each country in two waves – July to August 2017 and August to September 2018 – with a sample size of approximately 12,000 for each.
The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
SOURCE: Hammond D et al. BMJ 2019 Jun 19. doi: 10.1136/bmj.l2219.
FROM THE BMJ
Key clinical point: Recent increases in vaping prevalence among teens “might be indicative of nicotine addiction.”
Major finding: Vaping prevalence increased from 11% to 16% in the United States and from 8% to 14.6% in Canada.
Study details: Two waves of a national, cross-sectional survey that included approximately 12,000 respondents each.
Disclosures: The study was funded by the U.S. National Institutes of Health. Dr. Hammond is supported by a Canadian Institutes of Health Research–Public Health Agency of Canada applied public health research chair. The investigators said that they had no other financial disclosures to report, but several have served as paid witnesses in legal challenges against tobacco companies.
Source: Hammond D et al. BMJ. 2019 Jun 19. doi: 10.1136/bmj.l2219.
Experts agree on routine lung disease screening in systemic sclerosis
MADRID – The for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.
“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.
Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).
“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.
There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.
In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.
The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.
“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.
ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.
The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.
“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.
Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.
SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.
MADRID – The for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.
“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.
Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).
“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.
There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.
In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.
The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.
“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.
ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.
The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.
“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.
Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.
SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.
MADRID – The for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.
“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.
Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).
“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.
There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.
In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.
The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.
“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.
ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.
The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.
“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.
Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.
SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.
REPORTING FROM EULAR 2019 Congress
Adjuvant corticosteroids in hospitalized patients with CAP
When is it appropriate to treat?
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
When is it appropriate to treat?
When is it appropriate to treat?
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
Case
A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.
Brief overview of the issue
Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.1 The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.2 After discharge from the hospital, about 18% of patients are readmitted within 30 days.3 An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.
Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted4 and approximately 10% of hospitalized patients with CAP require ICU admission.5 Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.5 Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
Overview of the data
The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.5 There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.6 Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.
The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.7 In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.7
The IDSA meta-analysis was similar and included 1,506 patients from six trials.8 In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.
The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.9
In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.10 Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.
The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.11
Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.12
Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
Application of the data to our patients
The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.
For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.13 Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
Bottom line
For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.
Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.
References
1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.
2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.
3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.
4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.
5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.
6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).
7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).
8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).
9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).
10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).
11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).
12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).
13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).
Key points
• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.
• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.
• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
QUIZ
Which of the following is FALSE regarding community acquired pneumonia?
A. CAP is the leading cause of infectious disease related death in the United States.
B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.
C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.
D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.
E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.
ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
Additional reading
Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).
Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).
Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).
Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.
Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
COPD exacerbations associated with poor sleep quality
in an 18-month prospective study of 480 patients.
“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”
The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).
At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).
Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.
Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.
The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”
The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.
SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.
in an 18-month prospective study of 480 patients.
“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”
The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).
At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).
Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.
Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.
The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”
The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.
SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.
in an 18-month prospective study of 480 patients.
“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”
The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).
At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).
Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.
Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.
The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”
The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.
SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.
FROM CHEST
Rivaroxaban tied to higher GI bleeding than other NOACs
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
SAN DIEGO – Patients on rivaroxaban had significantly higher rates of GI bleeding, compared with those taking apixaban or dabigatran, results from a large population-based study showed.
“This may be due to the fact that rivaroxaban is administered as a single daily dose as opposed to the other two non–vitamin K anticoagulants [NOACs], which are given twice daily,” lead study author Arnar B. Ingason said at the annual Digestive Disease Week. “This may lead to a greater variance in plasma drug concentration, making these patients more susceptible to bleeding.”
Mr. Ingason, a medical student at the University of Iceland, Reykjavik, said that although several studies have compared warfarin with NOACs, it remains unclear which NOAC has the most favorable GI profile. In an effort to improve the research in this area, he and his associates performed a nationwide, population-based study during March 2014–Jan. 2018 to compare the GI bleeding risk of patients receiving rivaroxaban to that of a combined pool of patients receiving either apixaban or dabigatran. They drew from the Icelandic Medicine Registry, which contains all outpatient drug prescriptions in the country. Next, the researchers linked the personal identification numbers of patients to the Landspitali University diagnoses registry, which includes more than 90% of all patients hospitalized for GI bleeding. They used 1:1 nearest neighbor propensity score for matching and Kaplan-Meier survival estimates and Cox regression to compare rates of GI bleeding. The study outcome of interest was any clinically relevant GI bleeding.
Mr. Ingason reported that the baseline characteristics were similar between the rivaroxaban group and the apixaban/dabigatran group. They matched for several variables, including age, sex, Charlson score, the proportion being anticoagulant naive, moderate to severe renal disease, moderate to severe liver disease, any prior bleeding, and any prior thrombotic events.
During the study period, 3,473 patients received rivaroxaban, 1,901 received apixaban, and 1,086 received dabigatran. After propensity score matching, the researchers compared 2,635 patients who received rivaroxaban with 2,365 patients who received either apixaban or dabigatran. They found that patients in the rivaroxaban group had significantly higher rates of GI bleeding, compared with in the apixaban/dabigatran group (1.2 and. 0.6 events per 100 patient-years, respectively). This yielded a hazard ratio of 2.02, “which means that patients receiving rivaroxaban are twice as likely to get GI bleeding compared to patients on apixaban or dabigatran,” Mr. Ingason said. When the researchers examined the entire unmatched cohort of patients, the rivaroxaban group also had significantly higher rates of GI bleeding, compared with the apixaban/dabigatran group (1.0 and 0.6 events per 100 patient-years; HR, 1.75).
Mr. Ingason and his colleagues observed that patients in the rivaroxaban group had higher rates of GI bleeding, compared with the apixaban/dabigatran group, during the entire follow-up period. At the end of year 4, the rivaroxaban group had a 4% cumulative event rate of GI bleeding, compared with 1.8% for the apixaban/dabigatran group, a highly significant difference at P = .0057).
When a meeting attendee asked Mr. Ingason why patients taking apixaban or dabigatran were combined into one group, he said that it was done to increase the power of their study. “Our theory was that rivaroxaban was different because it is administered as a single daily dose, while the others are given twice daily,” he said. The researchers reported having no financial disclosures.
REPORTING FROM DDW 2019
U.S. travelers to Europe need up to date measles immunization
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
FROM PEDIATRICS
Eosinophil-guided therapy reduces corticosteroid use in COPD
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
FROM LANCET RESPIRATORY MEDICINE
Endobronchial valves for lung volume reduction: What can we offer patients with advanced emphysema?
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
Clinical pulmonary medicine. Cardiovascular medicine and surgery. Chest infections. Interprofessional team.
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member