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ARDS incidence is declining. Is it a preventable syndrome?
TORONTO – The incidence of acute respiratory distress syndrome (ARDS) is on the decline, according to a retrospective, population-based cohort study conducted at the Mayo Clinic in Rochester, Minn.
“This is very promising data in combating this syndrome,” reported Augustin Joseph of the Mayo Clinic, and “it suggests that ARDS may in part be a completely preventable disease.”
To see if ARDS incidence has continued to decline, Mr. Joseph’s group studied all patients admitted during 2009-2014 to the Mayo Clinic’s ICU, the only facility in the county that cares for ARDS patients. From 82,388 ICU admissions, they identified 505 patients with ARDS according to the Berlin definition of ARDS developed in 2012.
The number of annual cases dropped from 108 in 2009 to 59 in 2014, and the incidence steadily declined from 74.5 cases per 100,000 in 2009 to 39.3 per 100,000 in 2014.
Median age was 67 years in 2009 and 62 years in 2014. Hospital mortality ranged from 15% to 26% during the study period, while hospital length of stay ranged from 8 to 15 days, with no clear decline in either.
“For hospital and ICU mortality and hospital and ICU length of stay, we did not see much difference [from 2009 to 2014], so the overall picture between the Guangxi Li study and mine was that we did not see much of a difference in the patients who had ARDS, but [in terms of] preventing ARDS, the incidence has continued to decline,” Mr. Joseph reported.
While the earlier study used the American-European Consensus Conference (AECC) definition of ARDS, Mr. Joseph and his colleagues diagnosed ARDS according to the Berlin definition. One of the major changes seen in the new Berlin rules is that acute lung injury no longer exists and patients with a P/F ratio (PaO2/FiO2 ratio, or the ratio of arterial oxygen partial pressure to fractional inspired oxygen) between 200 and 300 are now considered to have “mild ARDS,” Mr. Joseph explained. With the AECC definition, a P/F ratio in this range was classified as acute lung injury and only one less than 200 was considered ARDS.
The researchers are now trying to parse out how changing ARDS diagnosis and management at their institution might be contributing to declining incidence, said Mr. Joseph.
TORONTO – The incidence of acute respiratory distress syndrome (ARDS) is on the decline, according to a retrospective, population-based cohort study conducted at the Mayo Clinic in Rochester, Minn.
“This is very promising data in combating this syndrome,” reported Augustin Joseph of the Mayo Clinic, and “it suggests that ARDS may in part be a completely preventable disease.”
To see if ARDS incidence has continued to decline, Mr. Joseph’s group studied all patients admitted during 2009-2014 to the Mayo Clinic’s ICU, the only facility in the county that cares for ARDS patients. From 82,388 ICU admissions, they identified 505 patients with ARDS according to the Berlin definition of ARDS developed in 2012.
The number of annual cases dropped from 108 in 2009 to 59 in 2014, and the incidence steadily declined from 74.5 cases per 100,000 in 2009 to 39.3 per 100,000 in 2014.
Median age was 67 years in 2009 and 62 years in 2014. Hospital mortality ranged from 15% to 26% during the study period, while hospital length of stay ranged from 8 to 15 days, with no clear decline in either.
“For hospital and ICU mortality and hospital and ICU length of stay, we did not see much difference [from 2009 to 2014], so the overall picture between the Guangxi Li study and mine was that we did not see much of a difference in the patients who had ARDS, but [in terms of] preventing ARDS, the incidence has continued to decline,” Mr. Joseph reported.
While the earlier study used the American-European Consensus Conference (AECC) definition of ARDS, Mr. Joseph and his colleagues diagnosed ARDS according to the Berlin definition. One of the major changes seen in the new Berlin rules is that acute lung injury no longer exists and patients with a P/F ratio (PaO2/FiO2 ratio, or the ratio of arterial oxygen partial pressure to fractional inspired oxygen) between 200 and 300 are now considered to have “mild ARDS,” Mr. Joseph explained. With the AECC definition, a P/F ratio in this range was classified as acute lung injury and only one less than 200 was considered ARDS.
The researchers are now trying to parse out how changing ARDS diagnosis and management at their institution might be contributing to declining incidence, said Mr. Joseph.
TORONTO – The incidence of acute respiratory distress syndrome (ARDS) is on the decline, according to a retrospective, population-based cohort study conducted at the Mayo Clinic in Rochester, Minn.
“This is very promising data in combating this syndrome,” reported Augustin Joseph of the Mayo Clinic, and “it suggests that ARDS may in part be a completely preventable disease.”
To see if ARDS incidence has continued to decline, Mr. Joseph’s group studied all patients admitted during 2009-2014 to the Mayo Clinic’s ICU, the only facility in the county that cares for ARDS patients. From 82,388 ICU admissions, they identified 505 patients with ARDS according to the Berlin definition of ARDS developed in 2012.
The number of annual cases dropped from 108 in 2009 to 59 in 2014, and the incidence steadily declined from 74.5 cases per 100,000 in 2009 to 39.3 per 100,000 in 2014.
Median age was 67 years in 2009 and 62 years in 2014. Hospital mortality ranged from 15% to 26% during the study period, while hospital length of stay ranged from 8 to 15 days, with no clear decline in either.
“For hospital and ICU mortality and hospital and ICU length of stay, we did not see much difference [from 2009 to 2014], so the overall picture between the Guangxi Li study and mine was that we did not see much of a difference in the patients who had ARDS, but [in terms of] preventing ARDS, the incidence has continued to decline,” Mr. Joseph reported.
While the earlier study used the American-European Consensus Conference (AECC) definition of ARDS, Mr. Joseph and his colleagues diagnosed ARDS according to the Berlin definition. One of the major changes seen in the new Berlin rules is that acute lung injury no longer exists and patients with a P/F ratio (PaO2/FiO2 ratio, or the ratio of arterial oxygen partial pressure to fractional inspired oxygen) between 200 and 300 are now considered to have “mild ARDS,” Mr. Joseph explained. With the AECC definition, a P/F ratio in this range was classified as acute lung injury and only one less than 200 was considered ARDS.
The researchers are now trying to parse out how changing ARDS diagnosis and management at their institution might be contributing to declining incidence, said Mr. Joseph.
AT CHEST 2017
Key clinical point: The incidence of acute respiratory distress syndrome is declining, an indication that it may be preventable, according to researchers.
Major finding: The number of annual cases dropped from 108 in 2009 to 59 in 2014, and the incidence steadily declined from 74.5 cases per 100,000 in 2009 to 39.3 per 100,000 in 2014.
Data source: Retrospective, population-based cohort study of all (505) patients admitted to the ICU for ARDS at a single center.
Disclosures: The authors reported having no relevant disclosures.
VIDEO: Evidence mounts for pulmonary embolism benefit from catheter thrombolysis
TORONTO – Catheter-directed thrombolysis of pulmonary embolism using an ultrasound-assisted device led to significantly better outcomes in patients hospitalized for pulmonary embolism, compared with conventional systemic thrombolytic treatment, in a propensity score–adjusted analysis of nearly 3,400 patients.
Catheter-directed thrombolysis (CDT) “represents an opportunity to locally treat pulmonary embolism with significant thrombus burden with lower bleeding complications,” Abhishek Mishra, MD, said at the CHEST annual meeting. “I think we are underusing CDT,” said Dr. Mishra, a cardiovascular disease physician at Guthrie Robert Packer Hospital in Sayre, Pa.
Although one CDT device, the EKOS endovascular system that uses ultrasound to facilitate pulmonary embolism (PE) thrombolysis, received Food & Drug Administration approval for U.S. marketing in 2014, the trials that have compared it with systemic thrombolysis have been small, noted Dr. Mishra, and none have looked at whether CDT improves patient survival, compared with standard treatments. The largest report on CDT treatment of PE came from a single-arm, uncontrolled study with 150 patients who received ultrasound-facilitated CDT (JACC Cardiovasc Interv. 2015 Aug;8[10]:1382-92).
To better document the incremental benefit from CDT, Dr. Mishra and his associates used data collected by the Nationwide Readmissions Database during 2013 and 2014, both before and after a CDT device became available for U.S. use. From among 4,426 patients hospitalized with a primary diagnosis of PE and treated with thrombolytic therapy, they used propensity score matching to compare 2,256 patients treated with systemic thrombolysis with 1,128 matched patients treated with CDT using tissue plasminogen activator.
The analysis showed that in-hospital death was 15% in the systemic patients and 6% in the CDT group, a relative risk reduction of 63%, and 30-day readmissions occurred in 11% of the systemic patients and in 8% of those treated with CDT, a 30% relative risk reduction. Both were statistically significant differences for the study’s two primary endpoints, Dr. Mishra reported at the meeting. Rates of intracerebral hemorrhage and gastrointestinal bleeds were both numerically lower with CDT, and significantly lower for gastrointestinal bleeds.
The researchers also ran a multivariate analysis on their data that showed CDT was linked with significant relative reductions of about 60% for both in-hospital death and 30-day readmissions, compared with patients on systemic therapy. The results Dr. Mishra reported also appeared in a published report (Am J Cardiol. 2017 Nov 1;120[9]:1653-61).
These findings help buttress the case for using CDT for at least some PE patients. “The key is which patients need it. What is the best way to stratify patients?” commented Victor F. Tapson, MD, a pulmonologist at Cedars-Sinai Medical Center in Los Angeles.
“Patients with PE and a normal right ventricle generally don’t need anything more aggressive than anticoagulation, and really sick patients with massive PE need systemic thrombolytics. Intermediate-risk patients” are best suited to CDT, but “the problem is that intermediate-risk patients are heterogeneous,” Dr. Tapson said in a video interview. Future studies should establish a more specific subgroup of intermediate-risk patients who benefit from routinely employed CDT, he suggested.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BY MITCHEL L. ZOLER
Frontline Medical News
BY MITCHEL L. ZOLER
Frontline Medical News
BY MITCHEL L. ZOLER
Frontline Medical News
TORONTO – Catheter-directed thrombolysis of pulmonary embolism using an ultrasound-assisted device led to significantly better outcomes in patients hospitalized for pulmonary embolism, compared with conventional systemic thrombolytic treatment, in a propensity score–adjusted analysis of nearly 3,400 patients.
Catheter-directed thrombolysis (CDT) “represents an opportunity to locally treat pulmonary embolism with significant thrombus burden with lower bleeding complications,” Abhishek Mishra, MD, said at the CHEST annual meeting. “I think we are underusing CDT,” said Dr. Mishra, a cardiovascular disease physician at Guthrie Robert Packer Hospital in Sayre, Pa.
Although one CDT device, the EKOS endovascular system that uses ultrasound to facilitate pulmonary embolism (PE) thrombolysis, received Food & Drug Administration approval for U.S. marketing in 2014, the trials that have compared it with systemic thrombolysis have been small, noted Dr. Mishra, and none have looked at whether CDT improves patient survival, compared with standard treatments. The largest report on CDT treatment of PE came from a single-arm, uncontrolled study with 150 patients who received ultrasound-facilitated CDT (JACC Cardiovasc Interv. 2015 Aug;8[10]:1382-92).
To better document the incremental benefit from CDT, Dr. Mishra and his associates used data collected by the Nationwide Readmissions Database during 2013 and 2014, both before and after a CDT device became available for U.S. use. From among 4,426 patients hospitalized with a primary diagnosis of PE and treated with thrombolytic therapy, they used propensity score matching to compare 2,256 patients treated with systemic thrombolysis with 1,128 matched patients treated with CDT using tissue plasminogen activator.
The analysis showed that in-hospital death was 15% in the systemic patients and 6% in the CDT group, a relative risk reduction of 63%, and 30-day readmissions occurred in 11% of the systemic patients and in 8% of those treated with CDT, a 30% relative risk reduction. Both were statistically significant differences for the study’s two primary endpoints, Dr. Mishra reported at the meeting. Rates of intracerebral hemorrhage and gastrointestinal bleeds were both numerically lower with CDT, and significantly lower for gastrointestinal bleeds.
The researchers also ran a multivariate analysis on their data that showed CDT was linked with significant relative reductions of about 60% for both in-hospital death and 30-day readmissions, compared with patients on systemic therapy. The results Dr. Mishra reported also appeared in a published report (Am J Cardiol. 2017 Nov 1;120[9]:1653-61).
These findings help buttress the case for using CDT for at least some PE patients. “The key is which patients need it. What is the best way to stratify patients?” commented Victor F. Tapson, MD, a pulmonologist at Cedars-Sinai Medical Center in Los Angeles.
“Patients with PE and a normal right ventricle generally don’t need anything more aggressive than anticoagulation, and really sick patients with massive PE need systemic thrombolytics. Intermediate-risk patients” are best suited to CDT, but “the problem is that intermediate-risk patients are heterogeneous,” Dr. Tapson said in a video interview. Future studies should establish a more specific subgroup of intermediate-risk patients who benefit from routinely employed CDT, he suggested.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Catheter-directed thrombolysis of pulmonary embolism using an ultrasound-assisted device led to significantly better outcomes in patients hospitalized for pulmonary embolism, compared with conventional systemic thrombolytic treatment, in a propensity score–adjusted analysis of nearly 3,400 patients.
Catheter-directed thrombolysis (CDT) “represents an opportunity to locally treat pulmonary embolism with significant thrombus burden with lower bleeding complications,” Abhishek Mishra, MD, said at the CHEST annual meeting. “I think we are underusing CDT,” said Dr. Mishra, a cardiovascular disease physician at Guthrie Robert Packer Hospital in Sayre, Pa.
Although one CDT device, the EKOS endovascular system that uses ultrasound to facilitate pulmonary embolism (PE) thrombolysis, received Food & Drug Administration approval for U.S. marketing in 2014, the trials that have compared it with systemic thrombolysis have been small, noted Dr. Mishra, and none have looked at whether CDT improves patient survival, compared with standard treatments. The largest report on CDT treatment of PE came from a single-arm, uncontrolled study with 150 patients who received ultrasound-facilitated CDT (JACC Cardiovasc Interv. 2015 Aug;8[10]:1382-92).
To better document the incremental benefit from CDT, Dr. Mishra and his associates used data collected by the Nationwide Readmissions Database during 2013 and 2014, both before and after a CDT device became available for U.S. use. From among 4,426 patients hospitalized with a primary diagnosis of PE and treated with thrombolytic therapy, they used propensity score matching to compare 2,256 patients treated with systemic thrombolysis with 1,128 matched patients treated with CDT using tissue plasminogen activator.
The analysis showed that in-hospital death was 15% in the systemic patients and 6% in the CDT group, a relative risk reduction of 63%, and 30-day readmissions occurred in 11% of the systemic patients and in 8% of those treated with CDT, a 30% relative risk reduction. Both were statistically significant differences for the study’s two primary endpoints, Dr. Mishra reported at the meeting. Rates of intracerebral hemorrhage and gastrointestinal bleeds were both numerically lower with CDT, and significantly lower for gastrointestinal bleeds.
The researchers also ran a multivariate analysis on their data that showed CDT was linked with significant relative reductions of about 60% for both in-hospital death and 30-day readmissions, compared with patients on systemic therapy. The results Dr. Mishra reported also appeared in a published report (Am J Cardiol. 2017 Nov 1;120[9]:1653-61).
These findings help buttress the case for using CDT for at least some PE patients. “The key is which patients need it. What is the best way to stratify patients?” commented Victor F. Tapson, MD, a pulmonologist at Cedars-Sinai Medical Center in Los Angeles.
“Patients with PE and a normal right ventricle generally don’t need anything more aggressive than anticoagulation, and really sick patients with massive PE need systemic thrombolytics. Intermediate-risk patients” are best suited to CDT, but “the problem is that intermediate-risk patients are heterogeneous,” Dr. Tapson said in a video interview. Future studies should establish a more specific subgroup of intermediate-risk patients who benefit from routinely employed CDT, he suggested.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: Catheter-directed thrombolysis cut in-hospital mortality by 63%, compared with conventional systemic thrombolysis.
Data source: The National Readmission Database, which included 4,426 patients hospitalized during 2013 and 2014 with primary pulmonary embolism and treated with thrombolysis.
Disclosures: Dr. Mishra had no disclosures. Dr. Tapson has been a consultant to and had received research funding from Ekos/BTG, a company that markets a catheter-directed thrombolysis device. He has also ties to Daiichi Sankyo, Inari, Janssen, and Portola.
VIDEO: Revised guidelines raise lung cancer screening age ceiling
TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.
This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).
“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.
Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.
The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.
The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.
The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCOM2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).
“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.
The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.
People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.
In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.
The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”
On Twitter @mitchelzoler
M. Patricia Rivera, MD, FCCP, comments: The revised ACCP screening guidelines recommend expanding the screening age from 55-74 years (age criterion used in the National Lung Screening Trial) to 55-77 years. While this may be interpreted as raising the screening age ceiling, the new recommendation is in line with the age range approved by Medicare. We should also keep in mind that after modeling studies to predict the benefits and harms of screening programs using different screening intervals, age ranges, and smoking histories (duration and time since quitting), the USPSTF concluded in their final recommendation that screening adults aged 55-80 years with same smoking history and time since quitting used in the National Lung Screening Trial (NLST) had a reasonable balance of benefits and harms. Implementing lung cancer screening has been challenging, and studies have reported many patient-, provider-, and system-based barriers including conflicting upper age range recommendations. 
While age and smoking history are important in identifying individuals at risk for lung cancer, development of lung cancer is likely multifactorial and several other risk factors need to be considered. The ACCP's revised guidelines provide flexibility when evaluating patients who do not meet the age and smoking history criteria for screening but who have a high risk for developing lung cancer based on risk prediction models. Following publication of the NLST results, secondary analysis of the data using a risk prediction model that takes into account additional risk factors for the development of lung cancer (race, COPD, and family history of lung cancer, among others) suggests risk prediction modeling may be helpful at identifying the individuals who are at highest risk for developing lung cancer. As pointed out by Dr. Mazzone and Dr. Silvestri, the ACCP lung cancer screening guidelines promote the expansion of lung cancer screening in a safe and effective way and encourage individualized risk profiling to aid in the selection of all individuals who will benefit from lung cancer screening.
M. Patricia Rivera, MD, FCCP, comments: The revised ACCP screening guidelines recommend expanding the screening age from 55-74 years (age criterion used in the National Lung Screening Trial) to 55-77 years. While this may be interpreted as raising the screening age ceiling, the new recommendation is in line with the age range approved by Medicare. We should also keep in mind that after modeling studies to predict the benefits and harms of screening programs using different screening intervals, age ranges, and smoking histories (duration and time since quitting), the USPSTF concluded in their final recommendation that screening adults aged 55-80 years with same smoking history and time since quitting used in the National Lung Screening Trial (NLST) had a reasonable balance of benefits and harms. Implementing lung cancer screening has been challenging, and studies have reported many patient-, provider-, and system-based barriers including conflicting upper age range recommendations.
While age and smoking history are important in identifying individuals at risk for lung cancer, development of lung cancer is likely multifactorial and several other risk factors need to be considered. The ACCP's revised guidelines provide flexibility when evaluating patients who do not meet the age and smoking history criteria for screening but who have a high risk for developing lung cancer based on risk prediction models. Following publication of the NLST results, secondary analysis of the data using a risk prediction model that takes into account additional risk factors for the development of lung cancer (race, COPD, and family history of lung cancer, among others) suggests risk prediction modeling may be helpful at identifying the individuals who are at highest risk for developing lung cancer. As pointed out by Dr. Mazzone and Dr. Silvestri, the ACCP lung cancer screening guidelines promote the expansion of lung cancer screening in a safe and effective way and encourage individualized risk profiling to aid in the selection of all individuals who will benefit from lung cancer screening.
M. Patricia Rivera, MD, FCCP, comments: The revised ACCP screening guidelines recommend expanding the screening age from 55-74 years (age criterion used in the National Lung Screening Trial) to 55-77 years. While this may be interpreted as raising the screening age ceiling, the new recommendation is in line with the age range approved by Medicare. We should also keep in mind that after modeling studies to predict the benefits and harms of screening programs using different screening intervals, age ranges, and smoking histories (duration and time since quitting), the USPSTF concluded in their final recommendation that screening adults aged 55-80 years with same smoking history and time since quitting used in the National Lung Screening Trial (NLST) had a reasonable balance of benefits and harms. Implementing lung cancer screening has been challenging, and studies have reported many patient-, provider-, and system-based barriers including conflicting upper age range recommendations.
While age and smoking history are important in identifying individuals at risk for lung cancer, development of lung cancer is likely multifactorial and several other risk factors need to be considered. The ACCP's revised guidelines provide flexibility when evaluating patients who do not meet the age and smoking history criteria for screening but who have a high risk for developing lung cancer based on risk prediction models. Following publication of the NLST results, secondary analysis of the data using a risk prediction model that takes into account additional risk factors for the development of lung cancer (race, COPD, and family history of lung cancer, among others) suggests risk prediction modeling may be helpful at identifying the individuals who are at highest risk for developing lung cancer. As pointed out by Dr. Mazzone and Dr. Silvestri, the ACCP lung cancer screening guidelines promote the expansion of lung cancer screening in a safe and effective way and encourage individualized risk profiling to aid in the selection of all individuals who will benefit from lung cancer screening.
TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.
This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).
“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.
Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.
The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.
The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.
The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCOM2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).
“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.
The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.
People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.
In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.
The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”
On Twitter @mitchelzoler
TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.
This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).
“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.
Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.
The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.
The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.
The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCOM2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).
“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.
The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.
People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.
In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.
The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”
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EXPERT ANALYSIS FROM CHEST 2017
Omalizumab helps asthma COPD overlap patients
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
AT CHEST 2017
Key clinical point: In patients with asthma COPD overlap (ACO), treatment with omalizumab was associated with decreased asthma exacerbations and improved symptom control, similar to that seen in non-ACO asthma patients.
Major finding: Asthma exacerbation numbers were reduced from baseline levels though month 12, from 3 or more exacerbations in both ACO and non ACO groups to 1.1 or less.
Data source: Subgroup analysis from a prospective observational study of omalizumab that focused on 78 patients (from 737 total) that had asthma and comorbid COPD according to one of two definitions.
Disclosures: Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Genentech sponsored the study and employs three of the investigators.
Nebulized LABA safe for long-term use in COPD
TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.
The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.
This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.
Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.
Formoterol significantly improved trough forced expiratory volume in 1 second (FEV1), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.
Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.
In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”
The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.
Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.
TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.
The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.
This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.
Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.
Formoterol significantly improved trough forced expiratory volume in 1 second (FEV1), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.
Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.
In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”
The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.
Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.
TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.
The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.
This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.
Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.
Formoterol significantly improved trough forced expiratory volume in 1 second (FEV1), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.
Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.
In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”
The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.
Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.
AT CHEST 2017
Key clinical point: The long-term safety of formoterol fumarate inhaled solution was confirmed in an FDA-mandated randomized trial in patients with moderate to severe COPD.
Major finding: Formoterol fumarate was noninferior to placebo for the primary safety endpoint of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.
Data source: Multicenter, randomized, double-blind, placebo-controlled trial including 1,071 patients with moderate or severe COPD, with at least one exacerbation recorded in the last year.
Disclosures: Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.
Nebulized glycopyrrolate improves lung function in COPD
TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*
There are currently no nebulized LAMAs approved for use in the U.S.
Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.
Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.
Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.
The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.
Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.
“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.
GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.
Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.
Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.
*This article was updated on Nov. 6, 2017.
Eric Gartman, MD, FCCP, comments: If approved, this would represent the first nebulized LAMA available in the U.S. – so in the small population of patients that is unable to utilize standard delivery devices, this would provide an option. It is unclear if this medication must be administered via the proprietary nebulizer that was used in the study – but if so, this would certainly add to the already extremely high cost of respiratory medications and further limit access for many patients. 
Eric Gartman, MD, FCCP, comments: If approved, this would represent the first nebulized LAMA available in the U.S. – so in the small population of patients that is unable to utilize standard delivery devices, this would provide an option. It is unclear if this medication must be administered via the proprietary nebulizer that was used in the study – but if so, this would certainly add to the already extremely high cost of respiratory medications and further limit access for many patients.
Eric Gartman, MD, FCCP, comments: If approved, this would represent the first nebulized LAMA available in the U.S. – so in the small population of patients that is unable to utilize standard delivery devices, this would provide an option. It is unclear if this medication must be administered via the proprietary nebulizer that was used in the study – but if so, this would certainly add to the already extremely high cost of respiratory medications and further limit access for many patients.
TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*
There are currently no nebulized LAMAs approved for use in the U.S.
Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.
Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.
Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.
The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.
Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.
“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.
GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.
Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.
Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.
*This article was updated on Nov. 6, 2017.
TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*
There are currently no nebulized LAMAs approved for use in the U.S.
Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.
Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.
Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.
The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.
Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.
“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.
GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.
Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.
Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.
*This article was updated on Nov. 6, 2017.
AT CHEST 2017
Key clinical point: Nebulized glycopyrrolate improved lung function and was well tolerated irrespective of baseline lung function or age.
Major finding: Statistically and clinically meaningful improvements in trough FEV1 at 12 weeks were seen in individuals, regardless of their baseline FEV1 % predicted.
Data source: Pooled findings from 2 RCTs, GOLDEN 3 and GOLDEN 4, that together included 1,294 moderate-to-very severe COPD patients.
Disclosures: Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.
Remimazolam surpasses midazolam for bronchoscopy sedation
TORONTO – An investigational sedative, remimazolam, that’s similar to midazolam but with faster onset and offset, resulted in significantly better procedural success compared with midazolam in a multicenter, phase III trial with 431 patients.
The results also showed that remimazolam was as safe as midazolam (Versed), with a very similar adverse event profile, said Gerard A. Silvestri, MD, FCCP, at the CHEST annual meeting.
The bronchoscopy trial enrolled patients at any of 15 U.S. centers with an American Society of Anesthesiologists (ASA) physical status classification of I-III and scheduled for diagnostic or therapeutic bronchoscopy. The enrolled patients averaged 62 years of age, and 38% were in ASA class III.
All patients received initial sedation treatment with fentanyl, followed by a three-to-one randomization to blinded remimazolam, blinded placebo that included midazolam rescue, or open-label midazolam. The study’s primary efficacy endpoint was procedural success, defined as patients who underwent the complete procedure without need for an alternative sedative and without need for more than five doses of the patient’s assigned medication within any 15 minute period during the procedure or need for more than three midazolam doses within any 12-minute period in the patients randomized to receive midazolam.
This primary endpoint occurred in 83% of 303 patients in the remimazolam arm, 5% of 59 patients in the placebo arm, and 34% of 69 patients in the midazolam arm, a statistically significant difference between the remimazolam patients and each of the comparator groups, reported Dr. Silvestri, a professor of medicine and a lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
The results also demonstrated the faster inset and offset of remimazolam. Treatment achieved adequate sedation to start the procedure after a median of 5 minutes with remimazolam, a median of 15.5 minutes with midazolam, and a median of 17 minutes among patients in the placebo group. Once sedation finished, patients returned to being fully alert after a median of 6 minutes with remimazolam, a median of 12 minutes with midazolam, and a median of 13.5 minutes for patients in the placebo arm.
“What’s nice about remimazolam is that the adverse event profile is exactly the same as with placebo and midazolam, and you have a reversal agent,” the same as what’s used for midazolam, he said.
Dr. Silvestri suggested several additional studies he would like to see run on remimazolam to better understand its clinical performance and role. These include studying the drug in the elderly, patients with an ASA classification of IV, obese patients, and those on high narcotic doses. He also suggested comparing remimazolam directly with propofol, testing remimazolam as a stand-alone agent without fentanyl co-administration, and trying the drug during other pulmonary procedures such as pleural-catheter placement and other invasive procedures, and in ICU patients.
The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – An investigational sedative, remimazolam, that’s similar to midazolam but with faster onset and offset, resulted in significantly better procedural success compared with midazolam in a multicenter, phase III trial with 431 patients.
The results also showed that remimazolam was as safe as midazolam (Versed), with a very similar adverse event profile, said Gerard A. Silvestri, MD, FCCP, at the CHEST annual meeting.
The bronchoscopy trial enrolled patients at any of 15 U.S. centers with an American Society of Anesthesiologists (ASA) physical status classification of I-III and scheduled for diagnostic or therapeutic bronchoscopy. The enrolled patients averaged 62 years of age, and 38% were in ASA class III.
All patients received initial sedation treatment with fentanyl, followed by a three-to-one randomization to blinded remimazolam, blinded placebo that included midazolam rescue, or open-label midazolam. The study’s primary efficacy endpoint was procedural success, defined as patients who underwent the complete procedure without need for an alternative sedative and without need for more than five doses of the patient’s assigned medication within any 15 minute period during the procedure or need for more than three midazolam doses within any 12-minute period in the patients randomized to receive midazolam.
This primary endpoint occurred in 83% of 303 patients in the remimazolam arm, 5% of 59 patients in the placebo arm, and 34% of 69 patients in the midazolam arm, a statistically significant difference between the remimazolam patients and each of the comparator groups, reported Dr. Silvestri, a professor of medicine and a lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
The results also demonstrated the faster inset and offset of remimazolam. Treatment achieved adequate sedation to start the procedure after a median of 5 minutes with remimazolam, a median of 15.5 minutes with midazolam, and a median of 17 minutes among patients in the placebo group. Once sedation finished, patients returned to being fully alert after a median of 6 minutes with remimazolam, a median of 12 minutes with midazolam, and a median of 13.5 minutes for patients in the placebo arm.
“What’s nice about remimazolam is that the adverse event profile is exactly the same as with placebo and midazolam, and you have a reversal agent,” the same as what’s used for midazolam, he said.
Dr. Silvestri suggested several additional studies he would like to see run on remimazolam to better understand its clinical performance and role. These include studying the drug in the elderly, patients with an ASA classification of IV, obese patients, and those on high narcotic doses. He also suggested comparing remimazolam directly with propofol, testing remimazolam as a stand-alone agent without fentanyl co-administration, and trying the drug during other pulmonary procedures such as pleural-catheter placement and other invasive procedures, and in ICU patients.
The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – An investigational sedative, remimazolam, that’s similar to midazolam but with faster onset and offset, resulted in significantly better procedural success compared with midazolam in a multicenter, phase III trial with 431 patients.
The results also showed that remimazolam was as safe as midazolam (Versed), with a very similar adverse event profile, said Gerard A. Silvestri, MD, FCCP, at the CHEST annual meeting.
The bronchoscopy trial enrolled patients at any of 15 U.S. centers with an American Society of Anesthesiologists (ASA) physical status classification of I-III and scheduled for diagnostic or therapeutic bronchoscopy. The enrolled patients averaged 62 years of age, and 38% were in ASA class III.
All patients received initial sedation treatment with fentanyl, followed by a three-to-one randomization to blinded remimazolam, blinded placebo that included midazolam rescue, or open-label midazolam. The study’s primary efficacy endpoint was procedural success, defined as patients who underwent the complete procedure without need for an alternative sedative and without need for more than five doses of the patient’s assigned medication within any 15 minute period during the procedure or need for more than three midazolam doses within any 12-minute period in the patients randomized to receive midazolam.
This primary endpoint occurred in 83% of 303 patients in the remimazolam arm, 5% of 59 patients in the placebo arm, and 34% of 69 patients in the midazolam arm, a statistically significant difference between the remimazolam patients and each of the comparator groups, reported Dr. Silvestri, a professor of medicine and a lung cancer pulmonologist at the Medical University of South Carolina in Charleston.
The results also demonstrated the faster inset and offset of remimazolam. Treatment achieved adequate sedation to start the procedure after a median of 5 minutes with remimazolam, a median of 15.5 minutes with midazolam, and a median of 17 minutes among patients in the placebo group. Once sedation finished, patients returned to being fully alert after a median of 6 minutes with remimazolam, a median of 12 minutes with midazolam, and a median of 13.5 minutes for patients in the placebo arm.
“What’s nice about remimazolam is that the adverse event profile is exactly the same as with placebo and midazolam, and you have a reversal agent,” the same as what’s used for midazolam, he said.
Dr. Silvestri suggested several additional studies he would like to see run on remimazolam to better understand its clinical performance and role. These include studying the drug in the elderly, patients with an ASA classification of IV, obese patients, and those on high narcotic doses. He also suggested comparing remimazolam directly with propofol, testing remimazolam as a stand-alone agent without fentanyl co-administration, and trying the drug during other pulmonary procedures such as pleural-catheter placement and other invasive procedures, and in ICU patients.
The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: The rate of successful bronchoscopies was 83% with remimazolam, 34% with midazolam, and 5% with placebo.
Data source: A multicenter, phase III trial with 431 patients.
Disclosures: The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.
IGRA preferred test for latent TB diagnosis
TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.
Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.
Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.
While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.
Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.
Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”
Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.
One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.
To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.
“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”
The authors reported there were no product or funding disclosures relevant to this study.
TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.
Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.
Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.
While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.
Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.
Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”
Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.
One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.
To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.
“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”
The authors reported there were no product or funding disclosures relevant to this study.
TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.
Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.
Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.
While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.
Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.
Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”
Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.
One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.
To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.
“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”
The authors reported there were no product or funding disclosures relevant to this study.
AT CHEST 2017
Key clinical point: Most physicians queried preferred IGRAs over TST for the detection of latent TB infection.
Major finding: Of the 304 respondents to a survey, 78% said they preferred IGRAs over TST for TB testing and 91% reported having a good understanding of how to use and interpret IGRAs.
Data source: Online survey of 304 pulmonary and infectious disease attending physicians and fellows from U.S.-based academic programs.
Disclosures: The authors reported there were no product or funding disclosures relevant to this study.
VIDEO: Balanced crystalloids protect kidney better than saline
TORONTO – Treatment with balanced crystalloid IV fluids cut adverse renal events modestly but with statistical significance, compared with 0.9% saline in hospitalized patients in a pair of single-center randomized trials with more than 29,000 total patients.
Despite showing a number needed to treat with balanced crystalloids of roughly 100 to prevent one major renal event, compared with saline, the scope of IV fluid use makes even this relatively small improvement potentially important to tens of thousands of patients annually.
“It’s a small but clinically important difference,” Wesley H. Self, MD, said at the CHEST annual meeting.
“These fluids are used every day and in millions of patients annually in the United States and worldwide. There is no functional cost difference between them, and now we have the data to show that [balanced crystalloid fluids] produce a better patient outcome. It’s reasonable to consider changing practice,” based on the results, said Matthew W. Semler, MD, a pulmonologist at Vanderbilt University Medical Center in Nashville, Tenn., who led one of the two trials.
At Vanderbilt, where the two studies ran, “we’ve changed our practice and are transitioning from primarily using saline to primarily balanced crystalloid,” Dr. Semler said in a video interview. The main limitation to changing practice now because of the results is that the two trials both ran at a single center.
The findings Dr. Semler reported came from the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), which randomized 7,860 ICU patients to treatment with 0.9% saline fluid and 7,942 ICU patients to treatment with balanced crystalloid fluid, either lactated Ringer’s or Plasma-Lyte A. The study’s primary endpoint was the combined 30-day rate of in-hospital death, incident need for renal replacement therapy, or at least a doubling of the patient’s baseline creatinine level, a marker of persistent renal dysfunction.
This outcome occurred in 14.3% of patients on balanced crystalloid fluid and 15.4% on saline, a 1.1% statistically significant absolute difference. The endpoint components showed that patients treated with balanced crystalloid had 0.8% less in-hospital death and 0.4% less incident renal replacement therapy; both of these between-group differences were close to having statistical significance. The two treatment groups showed less difference in the rate of persistent renal dysfunction.
The second trial had an identical design but ran instead in the emergency department. The Saline Against Lactated Ringers or Plasmalyte in the Emergency Department (SALT-ED) trial randomized 6,708 to receive balanced crystalloid and 6,639 to receive saline. The combined primary renal endpoint was 0.9% less frequent with balanced crystalloid fluid, a statistically significant difference, Dr. Self, an emergency medicine physician at Vanderbilt, reported at the meeting. In this study the between-group differences for both incident renal replacement therapy and persistent renal dysfunction were statistically significant in favor of balanced crystalloid, but the between-group mortality difference was not significantly different.
The reason why balanced crystalloid fluid produced better renal outcomes than saline remains unclear. Both Dr. Semler and Dr. Self noted that the two balanced crystalloid fluids used in the study have chloride levels that closely match normal plasma levels, but the chloride concentration in 0.9% saline is about 50% higher than plasma. Some researchers have hypothesized, based on animal findings, that this difference may influence inflammation, blood pressure, acute kidney injury, and renal vasoconstriction.
The SMART and SALT-ED trials received no commercial funding. Dr. Semler had no disclosures. Dr. Self has been a consultant to Abbott Point of Care, BioTest, Cempra, Ferring, Gilead, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Bennett P. deBoisblanc, MD , is professor of medicine at Louisiana State University Health and director of Critical Care Services at the Medical Center of Louisiana in New Orleans. He had no disclosures. He made these comments from the floor during discussion of the two reports.
Bennett P. deBoisblanc, MD , is professor of medicine at Louisiana State University Health and director of Critical Care Services at the Medical Center of Louisiana in New Orleans. He had no disclosures. He made these comments from the floor during discussion of the two reports.
Bennett P. deBoisblanc, MD , is professor of medicine at Louisiana State University Health and director of Critical Care Services at the Medical Center of Louisiana in New Orleans. He had no disclosures. He made these comments from the floor during discussion of the two reports.
TORONTO – Treatment with balanced crystalloid IV fluids cut adverse renal events modestly but with statistical significance, compared with 0.9% saline in hospitalized patients in a pair of single-center randomized trials with more than 29,000 total patients.
Despite showing a number needed to treat with balanced crystalloids of roughly 100 to prevent one major renal event, compared with saline, the scope of IV fluid use makes even this relatively small improvement potentially important to tens of thousands of patients annually.
“It’s a small but clinically important difference,” Wesley H. Self, MD, said at the CHEST annual meeting.
“These fluids are used every day and in millions of patients annually in the United States and worldwide. There is no functional cost difference between them, and now we have the data to show that [balanced crystalloid fluids] produce a better patient outcome. It’s reasonable to consider changing practice,” based on the results, said Matthew W. Semler, MD, a pulmonologist at Vanderbilt University Medical Center in Nashville, Tenn., who led one of the two trials.
At Vanderbilt, where the two studies ran, “we’ve changed our practice and are transitioning from primarily using saline to primarily balanced crystalloid,” Dr. Semler said in a video interview. The main limitation to changing practice now because of the results is that the two trials both ran at a single center.
The findings Dr. Semler reported came from the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), which randomized 7,860 ICU patients to treatment with 0.9% saline fluid and 7,942 ICU patients to treatment with balanced crystalloid fluid, either lactated Ringer’s or Plasma-Lyte A. The study’s primary endpoint was the combined 30-day rate of in-hospital death, incident need for renal replacement therapy, or at least a doubling of the patient’s baseline creatinine level, a marker of persistent renal dysfunction.
This outcome occurred in 14.3% of patients on balanced crystalloid fluid and 15.4% on saline, a 1.1% statistically significant absolute difference. The endpoint components showed that patients treated with balanced crystalloid had 0.8% less in-hospital death and 0.4% less incident renal replacement therapy; both of these between-group differences were close to having statistical significance. The two treatment groups showed less difference in the rate of persistent renal dysfunction.
The second trial had an identical design but ran instead in the emergency department. The Saline Against Lactated Ringers or Plasmalyte in the Emergency Department (SALT-ED) trial randomized 6,708 to receive balanced crystalloid and 6,639 to receive saline. The combined primary renal endpoint was 0.9% less frequent with balanced crystalloid fluid, a statistically significant difference, Dr. Self, an emergency medicine physician at Vanderbilt, reported at the meeting. In this study the between-group differences for both incident renal replacement therapy and persistent renal dysfunction were statistically significant in favor of balanced crystalloid, but the between-group mortality difference was not significantly different.
The reason why balanced crystalloid fluid produced better renal outcomes than saline remains unclear. Both Dr. Semler and Dr. Self noted that the two balanced crystalloid fluids used in the study have chloride levels that closely match normal plasma levels, but the chloride concentration in 0.9% saline is about 50% higher than plasma. Some researchers have hypothesized, based on animal findings, that this difference may influence inflammation, blood pressure, acute kidney injury, and renal vasoconstriction.
The SMART and SALT-ED trials received no commercial funding. Dr. Semler had no disclosures. Dr. Self has been a consultant to Abbott Point of Care, BioTest, Cempra, Ferring, Gilead, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Treatment with balanced crystalloid IV fluids cut adverse renal events modestly but with statistical significance, compared with 0.9% saline in hospitalized patients in a pair of single-center randomized trials with more than 29,000 total patients.
Despite showing a number needed to treat with balanced crystalloids of roughly 100 to prevent one major renal event, compared with saline, the scope of IV fluid use makes even this relatively small improvement potentially important to tens of thousands of patients annually.
“It’s a small but clinically important difference,” Wesley H. Self, MD, said at the CHEST annual meeting.
“These fluids are used every day and in millions of patients annually in the United States and worldwide. There is no functional cost difference between them, and now we have the data to show that [balanced crystalloid fluids] produce a better patient outcome. It’s reasonable to consider changing practice,” based on the results, said Matthew W. Semler, MD, a pulmonologist at Vanderbilt University Medical Center in Nashville, Tenn., who led one of the two trials.
At Vanderbilt, where the two studies ran, “we’ve changed our practice and are transitioning from primarily using saline to primarily balanced crystalloid,” Dr. Semler said in a video interview. The main limitation to changing practice now because of the results is that the two trials both ran at a single center.
The findings Dr. Semler reported came from the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), which randomized 7,860 ICU patients to treatment with 0.9% saline fluid and 7,942 ICU patients to treatment with balanced crystalloid fluid, either lactated Ringer’s or Plasma-Lyte A. The study’s primary endpoint was the combined 30-day rate of in-hospital death, incident need for renal replacement therapy, or at least a doubling of the patient’s baseline creatinine level, a marker of persistent renal dysfunction.
This outcome occurred in 14.3% of patients on balanced crystalloid fluid and 15.4% on saline, a 1.1% statistically significant absolute difference. The endpoint components showed that patients treated with balanced crystalloid had 0.8% less in-hospital death and 0.4% less incident renal replacement therapy; both of these between-group differences were close to having statistical significance. The two treatment groups showed less difference in the rate of persistent renal dysfunction.
The second trial had an identical design but ran instead in the emergency department. The Saline Against Lactated Ringers or Plasmalyte in the Emergency Department (SALT-ED) trial randomized 6,708 to receive balanced crystalloid and 6,639 to receive saline. The combined primary renal endpoint was 0.9% less frequent with balanced crystalloid fluid, a statistically significant difference, Dr. Self, an emergency medicine physician at Vanderbilt, reported at the meeting. In this study the between-group differences for both incident renal replacement therapy and persistent renal dysfunction were statistically significant in favor of balanced crystalloid, but the between-group mortality difference was not significantly different.
The reason why balanced crystalloid fluid produced better renal outcomes than saline remains unclear. Both Dr. Semler and Dr. Self noted that the two balanced crystalloid fluids used in the study have chloride levels that closely match normal plasma levels, but the chloride concentration in 0.9% saline is about 50% higher than plasma. Some researchers have hypothesized, based on animal findings, that this difference may influence inflammation, blood pressure, acute kidney injury, and renal vasoconstriction.
The SMART and SALT-ED trials received no commercial funding. Dr. Semler had no disclosures. Dr. Self has been a consultant to Abbott Point of Care, BioTest, Cempra, Ferring, Gilead, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: Balanced crystalloids reduced combined adverse renal events by 1.1% in ICU patients and 0.9% in ED patients.
Data source: The SMART and SALT-ED trials, both single-center studies with a total of 29,149 patients.
Disclosures: The SMART and SALT-ED trials received no commercial funding. Dr. Semler had no disclosures. Dr. Self has been a consultant to Abbott Point of Care, BioTest, Cempra, Ferring, Gilead, and Pfizer.
Cardiogenic shock boosts PAH readmissions 10-fold
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: Patients with cardiogenic shock following PAH hospitalization had a 9.7-fold increased rate of 30-day rehospitalization, compared with patients without shock.
Data source: The National Readmissions Database, which included 776 index U.S. hospitalizations for pulmonary arterial hospitalization during 2013.
Disclosures: Dr. Chatterjee had no disclosures.
