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More than 16% of ED sepsis patients not admitted to hospital
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
SAN DIEGO – More than 16% of emergency department sepsis patients are not admitted to the hospital, preliminary results from a large retrospective cohort study found.
“Nothing is really known about this topic,” lead study author Ithan D. Peltan, MD, said in an interview at an international conference of the American Thoracic Society. “In previous research, we’ve been focused on patients with sepsis who are admitted to the hospital. We have never thoroughly recognized that a fair number of patients who meet clinical criteria for sepsis in the emergency department are actually triaged to outpatient management. We don’t really know anything about these patients. What are their clinical characteristics and what are their outcomes like? And what are the factors that are leading them to be discharged from the ED rather than be admitted to the hospital?”
To find out, he and his associates retrospectively reviewed the medical records of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah between July 2013 and December 2016. They excluded trauma patients, those who left the ED against medical advice, those who were discharged to hospice or who died in the ED, and eligible patients’ repeat ED encounters. Patients transferred to another acute care facility were considered admitted, while transfers to non-acute care such as skilled nursing or psychiatric facilities were classified as discharges. Next, Dr. Peltan and his associates employed inverse probability weights using a propensity score for ED discharge based on age, sex, Charlson score, ED acuity score, initial ED vital signs, white blood cell count, lactate, sequential organ failure assessment (SOFA)score, busyness of the ED, and study hospital to compare 30-day mortality between patients admitted to the hospital versus those discharged from the ED.
Of the 12,002 patients included in the analysis, 10,032 (83.6%) were admitted, while 1,970 (16.4%) were discharged. Compared with admitted patients, discharged patients were younger (a mean of 53 vs. 60 years, respectively; P less than .001); more likely to be female (65% vs. 55%; P less than .001); more likely to be nonwhite or Hispanic (21% vs 17%; P less than .001), and had fewer comorbidities and physiologic derangements. In addition, crude mortality at 30 days was lower in discharged versus admitted patients (1.0% vs. 6.2%, respectively; P less than .001). After the propensity-adjusted analysis, there was no significant difference in 30-day mortality for discharged vs. admitted sepsis patients (adjusted odds ratio 1.0).
“We were worried that discharged ED sepsis patients were being mismanaged and weren’t going to do well as similar patients who were admitted to the hospital,” Dr. Peltan said. “This analysis is still a work in progress, but with that caveat, our findings so far suggest that physicians are making pretty good decisions overall.”
The researchers also found that, among 89 ED physicians who cared for 20 or more eligible patients, some did not discharge any of their sepsis patients, while others discharged 39% of their sepsis patients. “That was surprising,” Dr. Peltan said. “This could mean that some hospital sepsis admissions depend on physician practice style more than the patient’s condition or treatment needs.”
Researchers emphasized that they do not recommend routine outpatient management for individual sepsis patients. “Almost certainly, some of the discharged patients should have been admitted to the hospital.” Dr. Peltan said. “I think there’s still a lot of opportunity to understand who these patients are, understand why there is so much physician variation, and to develop tools to further optimize triage decisions.”
The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
SOURCE: Peltan ID et al. ATS 2018, Abstract A5994/702.
AT ATS 2018
Key clinical point: More research is needed to optimize triage decisions for ED sepsis patients and to understand possible disparities in ED disposition.
Major finding: Among adult patients who met clinical criteria for sepsis in the emergency department, 16.4% were not admitted to the hospital.
Study details: A retrospective study of 12,002 adult ED patients who met criteria for sepsis at two tertiary hospitals and two community hospitals in Utah.
Disclosures: The study was funded in part by the Intermountain Research and Medical Foundation in Salt Lake City. Dr. Peltan reported having no financial disclosures.
Source: Peltan ID et al. Abstract 5994/702, ATS 2018.
Noninvasive ventilation during exercise benefited a subgroup of COPD patients
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
SAN DIEGO – Use of noninvasive ventilation during an exercise session in hypercapnic patients with very severe chronic obstructive pulmonary disease (COPD) led to a clinically relevant increase in endurance time, a randomized trial showed.
At an international conference of the American Thoracic Society, lead study author Tessa Schneeberger noted that nocturnal noninvasive ventilation (NIV) in hypercapnic COPD patients has been shown to improve quality of life and survival (Lancet Resp Med. 2014;2[9]:698-705). Another study found that NIV with unchanged nocturnal settings during a 6-minute walk test in hypercapnic COPD patients can increase oxygenation, decrease dyspnea, and increase walking distance (Eur Respir J. 2007;29:930-6).
For the current study, Ms. Schneeberger, a physiotherapist at the Institute for Pulmonary Rehabilitation Research, Schoenau am Koenigssee, Germany, and her associates set out to investigate short-term effects of using NIV during exercise in hypercapnic patients with very severe COPD, as part of a 3-week inpatient physical rehabilitation program. The researchers limited their analysis to 20 Global Initiative for Chronic Obstructive Lung Disease stage IV patients aged 40-80 years with a carbon dioxide partial pressure (PCO2) of greater than 50 mm Hg at rest and/or during exercise and who were non-naive to NIV, and excluded patients with concomitant conditions that make cycling impossible, those with acute exacerbations, and those with exercise-limiting cardiovascular diseases.
The day after an initial incremental cycle ergometer test, patients performed two constant work rate tests (CWRT) at 60% of the peak work rate, with and without NIV, in randomized order and with a resting time of 1 hour between tests. The inspiratory positive airway pressure (IPAP) was individually adjusted from each patient’s nocturnal settings to provide sufficient pressure to relieve the work on breathing muscles and to decrease transcutaneous PCO2 (TcPCO2) levels during NIV. The primary outcome was cycle endurance time. Other outcomes of interest were TcPCO2, oxygen saturation (SpO2) and perceived dyspnea/leg fatigue via the 10-point Borg scale during CWRTs.
The mean age of the study participants was 60 years, their mean body mass index was 23 kg/m2, their mean forced expiratory volume in1 second was 19% predicted, their mean PaCO2 was 51 mm Hg, their mean PaO2 was 54.5 mm Hg, their mean distance on the 6-minute walk test was 243 meters, and their mean peak work rate was 42 watts.
NIV via full face mask and assisted pressure control ventilation mode was performed with mean IPAP/expiratory PAP levels of 27/6 cm H2O.
During CWRTs patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013) and one that was clinically relevant. At isotime (the time of CWRT with shortest duration), TcPCO2 was significantly lower with NIV (a mean of –6.1 mm Hg), while SpO2 was significantly higher with NIV (a mean of 3.6%). In addition, after CWRT, NIV patients perceived less dyspnea (P = .008) with comparable leg fatigue (P = .79).
“We found that NIV during cycling exercise in hypercapnic patients with very severe COPD can lead to an acutely significant increase in exercise duration, with lower TcPCO2 and a reduced sensation of dyspnea,” Ms. Schneeberger concluded. “It can be performed with high-pressure assisted-controlled ventilation comparable as that used nocturnally to effectively reduce TcPCO2 in people with COPD.”
She emphasized that this approach requires appropriate equipment and special staff expertise for setup titration. “We will continue this research to look into the underlying physiological mechanisms to define nonresponders and responders, and also to look how at this might improve outcomes of an exercise training program.”
Ms. Schneeberger reported having no financial disclosures.
SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.
REPORTING FROM ATS 2018
Key clinical point: Noninvasive ventilation (NIV) during exercise seems feasible and could provide an opportunity to improve endurance training outcomes in selected chronic obstructive pulmonary disease patients.
Major finding: During constant work rate tests patients cycled with NIV for 663 seconds and without NIV for 476 seconds, a significant difference (P = .013).
Study details: A randomized trial of short-term effects of NIV during exercise in 20 hypercapnic patients with very severe COPD.
Disclosures: Ms. Schneeberger reported having no financial disclosures.
Source: Schneeberger T et al. ATS 2018, Abstract A2453.
Effort to phenotype pulmonary hypertension patients under way
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
SAN DIEGO – A massive effort to better understand and treat patients with pulmonary hypertension and right heart dysfunction is underway.
The endeavor, funded by the National Heart, Lung, and Blood Institute and the Pulmonary Hypertension Association and known as Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS), began recruiting participants in 2017, with a goal of 1,500 by 2019. The aim is to perform comprehensive phenotyping and endophenotyping across the World Health Organization–classified pulmonary hypertension (PH) clinical groups 1 through 5 in order to deconstruct the traditional classification and define new meaningful subclassifications of patients with pulmonary vascular disease.
At an international conference of the American Thoracic Society, one of the study’s investigators, Robert P. Frantz, MD, discussed the role of echocardiography and MRI in the overall PVDOMICS program, which he characterized as a work in progress. “Imaging is critically important as we try to integrate severity of pulmonary vascular disease along with how well the ventricle functions as way to try and understand why some patients have a failing RV at a given pulmonary resistance and others don’t,” said Dr. Frantz, who directs the Mayo Pulmonary Hypertension Clinic in Rochester, Minn. The goals are to be able to integrate cardiac morphology and function with contemporaneous hemodynamics, he said. This will allow for validation of noninvasive hemodynamics versus right heart catheterization across all the phenotypes.
“In addition, we’ll have imaging parameters as predictors of hemodynamics at rest and with exercise, particularly in conditions like heart failure with preserved ejection fraction or concerns about left atrial stiffness,” he said. “In these cases, our ability on the basis of echocardiography or MRI to guess what the wedge pressure is at rest or exercise, or to think about other more recently described phenotypes like left atrial stiffness in patients who have left atrial ablation procedures, will be enabled by looking at parameters such as left atrial strain.”
Ultimately, he continued, a key goal of PVDOMICS is to be able to correlate the “-omics” with markers of RV compensation in an effort to understand what the determinants of RV compensation are across the varying types of pulmonary vascular disease.
“If we could do that, we might be able to develop new targets for therapy,” said Dr. Frantz. To illustrate how this might work, he cited findings from researchers who set out to identify and characterize homogeneous phenotypes by a cluster analysis in scleroderma patients with pulmonary hypertension, who were identified from two prospective cohorts in the United States and France (PLoS One 2018 May 15;13[5]:e0197112).
The researchers identified four different clusters of scleroderma patients: those with mild to moderate PAH with no or minimal interstitial lung disease and low-diffusing capacity for carbon monoxide; those with precapillary PH with severe ILD and worse survival; those with severe PAH, who trended toward worse survival, and those similar to the first cluster but with higher DLCO.
Dr. Frantz then shared preliminary findings of echocardiographic parameters by primary WHO group in PVDOMICS, on behalf of his PVDOMICS collaborators. They found, for example, that the mean right ventricular systolic pressure in group 3 was 45 mm Hg, as opposed to group 1, which was 64 mm Hg. “In general we had some patients in group 3 with less severe elevation of PA pressures,” he said.
Other parameters that can be compared across WHO groups include ventricular fractional area change, tricuspid annular plane systolic excursion, and RV free wall strain. “That strain of the right ventricle is one of the most important ways of looking at how the right ventricle works,” Dr. Frantz explained. “With this, we can integrate the concept of severity of RV dysfunction with severity of pulmonary vascular disease. This is where the rubber hits the road. It’s going to be very complicated and time consuming, but I think critically important. Ultimately, we can make proteomic heat maps that track these correlates, and ultimately identify pathways that may be driving RV compensation in pulmonary vascular disease.”
Dr. Frantz reported having no relevant financial disclosures.
AT ATS 2018
Lung volume reduction procedures on the rise since 2011
SAN DIEGO – The number of has been increasing since 2011, according to a large national analysis.
Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.
In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”
Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).
Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.
The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).
On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).
On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).
“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”
Dr. Attaway and her associates reported having no financial disclosures.
SOURCE: Attaway A et al. ATS 2018, Abstract 4436.
SAN DIEGO – The number of has been increasing since 2011, according to a large national analysis.
Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.
In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”
Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).
Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.
The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).
On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).
On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).
“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”
Dr. Attaway and her associates reported having no financial disclosures.
SOURCE: Attaway A et al. ATS 2018, Abstract 4436.
SAN DIEGO – The number of has been increasing since 2011, according to a large national analysis.
Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.
In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”
Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).
Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.
The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).
On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).
On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).
“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”
Dr. Attaway and her associates reported having no financial disclosures.
SOURCE: Attaway A et al. ATS 2018, Abstract 4436.
AT ATS 2018
Key clinical point: Lung volume–reduction surgery remains an evidence-based therapy for a cohort of severe COPD patients.
Major finding: Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).
Study details: A retrospective cohort analysis of 2,805 patients who underwent LVRS.
Disclosures: The researchers reported having no financial disclosures.
Source: Attaway A et al. Abstract 4436, ATS 2018.
Aclidinium bromide for COPD: No impact on MACE
SAN DIEGO – The use of aclidinium bromide 400 mcg b.i.d. did not increase the risk of major adverse cardiac events or mortality in patients with moderate to very severe , compared with placebo.
Those are two key findings from the ASCENT COPD trial presented by Robert A. Wise, MD, at an international conference of the American Thoracic Society. “Cardiovascular risk factors and comorbidities are prevalent in patients with COPD, and about 30% of COPD patients die of cardiovascular disease,” said Dr. Wise, who serves as director of research for the division of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, Baltimore. “However, patients who have cardiovascular disease are often excluded from, or not enrolled in, COPD clinical trials. Moreover, there has been controversy as to whether or not treatment with a long-acting muscarinic antagonist is associated with an increased risk of cardiovascular events. That’s been seen in randomized trials, meta-analyses, as well as in observational studies.”
Aclidinium bromide 400 mcg b.i.d., administered by the Pressair inhaler, is approved as a maintenance treatment for patients with COPD. However, during the registration studies, there were not an adequate number of cardiovascular events in order to ascertain clearly whether or not the drug was associated with increased risk, Dr. Wise said. Therefore, he and his associates in the ASCENT COPD study set out to assess the long-term cardiovascular safety profile of aclidinium 400 mcg b.i.d. in patients with moderate to very severe COPD at risk of major adverse cardiovascular events (MACE) for up to 3 years (Chronic Obstr Pulm Dis. 2018;5[1]:5-15). For the randomized, placebo-controlled, parallel-group study, patients received treatment with aclidinium bromide or a placebo inhaler of similar appearance. The study was designed to be terminated when at least 122 patients experienced an adjudicated MACE. The primary safety endpoint was time to first MACE during follow-up of up to 3 years, while the primary efficacy endpoint was the rate of moderate to severe exacerbations per patient per year during the first year of treatment.
To be included in the study, patients had to be at least 40 years of age with moderate to very severe stable COPD, have a smoking history of at least 10 pack-years, and have at least one of the following significant risk factors: cerebrovascular disease; coronary artery disease; peripheral vascular disease, or history of claudication; or at least two atherothrombotic risk factors (male at least 65 years of age, female at least 70 years of age; waist circumference of at least 40 inches among males or at least 38 inches among females; an estimated glomerular filtration rate of less than 60 mL/min and microalbuminuria; dyslipidemia; or hypertension).
The researchers randomized 1,791 patients to the aclidinium group and 1,798 to the placebo group. Their mean age was 67 years, and about 60% of patients had an exacerbation in the preceding year. Nearly two-thirds of patients (63%) were receiving concomitant long-acting beta 2-agonists (LABA) or LABA/inhaled corticosteroid therapy. In addition, 44% of patients entered the study with a history of a prior cardiovascular event plus at least two atherothrombotic risk factors, 52% reported at least two atherothrombotic risk factors without any prior cardiovascular events, and 4% had a history of a prior cardiovascular event only.
Dr. Wise reported that aclidinium did not increase the risk of MACE in patients with moderate to very severe COPD with significant cardiovascular risk factors, compared with placebo (hazard ratio 0.89; P = .469); non-inferiority was concluded as the upper bound of the 95% confidence interval was less than 1.8). In terms of all-cause mortality, aclidinium did not increase the risk of death, compared with placebo (HR 0.99; P = .929).
During the first year of treatment, Dr. Wise and his associates also observed a 22% reduction in COPD exacerbation rate for aclidinium vs. placebo groups (HR 0.44 vs. 0.57, respectively; P less than .001), and a 35% reduction in the rate of COPD exacerbations leading to hospitalizations (HR 0.07 vs. 0.10; P = .006). “The reduction in exacerbation risk was similar, whether or not patients had an exacerbation in the past year,” Dr. Wise said. He reported being a consultant to, and receiving research support from, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and ContraFect.
[email protected]
SOURCE: Wise, R., et al., Abstract 7711, ATS 2018.
SAN DIEGO – The use of aclidinium bromide 400 mcg b.i.d. did not increase the risk of major adverse cardiac events or mortality in patients with moderate to very severe , compared with placebo.
Those are two key findings from the ASCENT COPD trial presented by Robert A. Wise, MD, at an international conference of the American Thoracic Society. “Cardiovascular risk factors and comorbidities are prevalent in patients with COPD, and about 30% of COPD patients die of cardiovascular disease,” said Dr. Wise, who serves as director of research for the division of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, Baltimore. “However, patients who have cardiovascular disease are often excluded from, or not enrolled in, COPD clinical trials. Moreover, there has been controversy as to whether or not treatment with a long-acting muscarinic antagonist is associated with an increased risk of cardiovascular events. That’s been seen in randomized trials, meta-analyses, as well as in observational studies.”
Aclidinium bromide 400 mcg b.i.d., administered by the Pressair inhaler, is approved as a maintenance treatment for patients with COPD. However, during the registration studies, there were not an adequate number of cardiovascular events in order to ascertain clearly whether or not the drug was associated with increased risk, Dr. Wise said. Therefore, he and his associates in the ASCENT COPD study set out to assess the long-term cardiovascular safety profile of aclidinium 400 mcg b.i.d. in patients with moderate to very severe COPD at risk of major adverse cardiovascular events (MACE) for up to 3 years (Chronic Obstr Pulm Dis. 2018;5[1]:5-15). For the randomized, placebo-controlled, parallel-group study, patients received treatment with aclidinium bromide or a placebo inhaler of similar appearance. The study was designed to be terminated when at least 122 patients experienced an adjudicated MACE. The primary safety endpoint was time to first MACE during follow-up of up to 3 years, while the primary efficacy endpoint was the rate of moderate to severe exacerbations per patient per year during the first year of treatment.
To be included in the study, patients had to be at least 40 years of age with moderate to very severe stable COPD, have a smoking history of at least 10 pack-years, and have at least one of the following significant risk factors: cerebrovascular disease; coronary artery disease; peripheral vascular disease, or history of claudication; or at least two atherothrombotic risk factors (male at least 65 years of age, female at least 70 years of age; waist circumference of at least 40 inches among males or at least 38 inches among females; an estimated glomerular filtration rate of less than 60 mL/min and microalbuminuria; dyslipidemia; or hypertension).
The researchers randomized 1,791 patients to the aclidinium group and 1,798 to the placebo group. Their mean age was 67 years, and about 60% of patients had an exacerbation in the preceding year. Nearly two-thirds of patients (63%) were receiving concomitant long-acting beta 2-agonists (LABA) or LABA/inhaled corticosteroid therapy. In addition, 44% of patients entered the study with a history of a prior cardiovascular event plus at least two atherothrombotic risk factors, 52% reported at least two atherothrombotic risk factors without any prior cardiovascular events, and 4% had a history of a prior cardiovascular event only.
Dr. Wise reported that aclidinium did not increase the risk of MACE in patients with moderate to very severe COPD with significant cardiovascular risk factors, compared with placebo (hazard ratio 0.89; P = .469); non-inferiority was concluded as the upper bound of the 95% confidence interval was less than 1.8). In terms of all-cause mortality, aclidinium did not increase the risk of death, compared with placebo (HR 0.99; P = .929).
During the first year of treatment, Dr. Wise and his associates also observed a 22% reduction in COPD exacerbation rate for aclidinium vs. placebo groups (HR 0.44 vs. 0.57, respectively; P less than .001), and a 35% reduction in the rate of COPD exacerbations leading to hospitalizations (HR 0.07 vs. 0.10; P = .006). “The reduction in exacerbation risk was similar, whether or not patients had an exacerbation in the past year,” Dr. Wise said. He reported being a consultant to, and receiving research support from, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and ContraFect.
[email protected]
SOURCE: Wise, R., et al., Abstract 7711, ATS 2018.
SAN DIEGO – The use of aclidinium bromide 400 mcg b.i.d. did not increase the risk of major adverse cardiac events or mortality in patients with moderate to very severe , compared with placebo.
Those are two key findings from the ASCENT COPD trial presented by Robert A. Wise, MD, at an international conference of the American Thoracic Society. “Cardiovascular risk factors and comorbidities are prevalent in patients with COPD, and about 30% of COPD patients die of cardiovascular disease,” said Dr. Wise, who serves as director of research for the division of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, Baltimore. “However, patients who have cardiovascular disease are often excluded from, or not enrolled in, COPD clinical trials. Moreover, there has been controversy as to whether or not treatment with a long-acting muscarinic antagonist is associated with an increased risk of cardiovascular events. That’s been seen in randomized trials, meta-analyses, as well as in observational studies.”
Aclidinium bromide 400 mcg b.i.d., administered by the Pressair inhaler, is approved as a maintenance treatment for patients with COPD. However, during the registration studies, there were not an adequate number of cardiovascular events in order to ascertain clearly whether or not the drug was associated with increased risk, Dr. Wise said. Therefore, he and his associates in the ASCENT COPD study set out to assess the long-term cardiovascular safety profile of aclidinium 400 mcg b.i.d. in patients with moderate to very severe COPD at risk of major adverse cardiovascular events (MACE) for up to 3 years (Chronic Obstr Pulm Dis. 2018;5[1]:5-15). For the randomized, placebo-controlled, parallel-group study, patients received treatment with aclidinium bromide or a placebo inhaler of similar appearance. The study was designed to be terminated when at least 122 patients experienced an adjudicated MACE. The primary safety endpoint was time to first MACE during follow-up of up to 3 years, while the primary efficacy endpoint was the rate of moderate to severe exacerbations per patient per year during the first year of treatment.
To be included in the study, patients had to be at least 40 years of age with moderate to very severe stable COPD, have a smoking history of at least 10 pack-years, and have at least one of the following significant risk factors: cerebrovascular disease; coronary artery disease; peripheral vascular disease, or history of claudication; or at least two atherothrombotic risk factors (male at least 65 years of age, female at least 70 years of age; waist circumference of at least 40 inches among males or at least 38 inches among females; an estimated glomerular filtration rate of less than 60 mL/min and microalbuminuria; dyslipidemia; or hypertension).
The researchers randomized 1,791 patients to the aclidinium group and 1,798 to the placebo group. Their mean age was 67 years, and about 60% of patients had an exacerbation in the preceding year. Nearly two-thirds of patients (63%) were receiving concomitant long-acting beta 2-agonists (LABA) or LABA/inhaled corticosteroid therapy. In addition, 44% of patients entered the study with a history of a prior cardiovascular event plus at least two atherothrombotic risk factors, 52% reported at least two atherothrombotic risk factors without any prior cardiovascular events, and 4% had a history of a prior cardiovascular event only.
Dr. Wise reported that aclidinium did not increase the risk of MACE in patients with moderate to very severe COPD with significant cardiovascular risk factors, compared with placebo (hazard ratio 0.89; P = .469); non-inferiority was concluded as the upper bound of the 95% confidence interval was less than 1.8). In terms of all-cause mortality, aclidinium did not increase the risk of death, compared with placebo (HR 0.99; P = .929).
During the first year of treatment, Dr. Wise and his associates also observed a 22% reduction in COPD exacerbation rate for aclidinium vs. placebo groups (HR 0.44 vs. 0.57, respectively; P less than .001), and a 35% reduction in the rate of COPD exacerbations leading to hospitalizations (HR 0.07 vs. 0.10; P = .006). “The reduction in exacerbation risk was similar, whether or not patients had an exacerbation in the past year,” Dr. Wise said. He reported being a consultant to, and receiving research support from, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and ContraFect.
[email protected]
SOURCE: Wise, R., et al., Abstract 7711, ATS 2018.
AT ATS 2018
Key clinical point: Researchers found no increased risk of MACE in at-risk patients with COPD receiving aclidinium.
Major finding: MACE risk and mortality in COPD patients with significant cardiovascular risk given aclidinium bromide had a hazard ratio 0.89 (P = .469), compared to placebo.
Study details: A randomized, placebo-controlled, parallel-group study of 3,589 patients with moderate to very severe COPD at risk of major adverse cardiovascular events.
Disclosures: Dr. Wise reported being a consultant to, and receiving research support from, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and ContraFect.
Source: Wise, R. et al, ATS 2018, Abstract 7711.
Customized airway stents show promise in feasibility trial
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
SAN DIEGO – for whom conventional stents were not suitable or failed, results from a small study demonstrated.
“Anatomically complex airway stenosis remains a challenging situation,” lead study author Nicolas Guibert, MD, said at an international conference of the American Thoracic Society. “Conventional devices are either not suited or may result in a significant complication rate, including poor clinical tolerance, migration, or granulation tissue reaction due to lack of congruence.”
Dr. Guibert reported results from eight patients. Of these, three had posttransplant complex airway stenoses involving the bronchus intermedius. Each improved after placement of the customized stents. For example, one patient with vanishing bronchus intermedius syndrome experienced improvements in NYHA dyspnea score from 3 to 1, the VQ11 score from 22 to 11/55, and forced expiratory volume in 1 second (FEV1) from 70% to 107%. The stent was removed after 3 months. Meanwhile, a patient with localized malacia and stenosis of the right main bronchus experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 score from 27 to 15/55, and FEV1 from 70% to 102%. That person’s stent is still in place with no complications. Another patient with localized malacia and stenosis of the bronchus intermedius experienced improvements in FEV1 from 84% to 100%. That person’s device was removed after 3 months, with no residual stenosis.
A fourth patient underwent stent placement for localized malacia (cartilage ring rupture). That person experienced improvements in NYHA dyspnea score from 3 to 1, VQ11 from 23 to 15/55, and FEV1 from 66% to 92%, and peak flow from 49% to 82%. The device is still in place with no complications. A fifth patient received stent placement for extensive tracheobronchomalacia, but it had imperfect congruence and was removed after 3 months because it caused intense cough.
One patient with post-tracheotomy stenosis experienced improvements in NYHA dyspnea score from 3 to 0, VQ11 from 29 to 12/55, and peak flow from 45% to 81%. That person’s device is still in place, Dr. Guibert said. Two other patients treated for post-tracheotomy experienced stent migration (conventional stents also migrated in these two cases), despite good bronchoscopic congruence after placement.
“Tracheal diseases result in suboptimal congruence, probably due to higher respiratory variation,” Dr. Guibert said. “These devices need to be studied in less selected populations and the technology has to be improved.” He reported having no financial disclosures.
SOURCE: Guibert N et al. ATS 2018, Abstract 4433.
REPORTING FROM ATS 2018
Key clinical point: Customized, 3-D airway stents have the potential for improving tolerance and decreasing the complication rate.
Major finding: Congruence and outcomes tended to be better in stenoses involving the bronchial level (three of three, no complications).
Study details: A feasibility study of eight patients with nonmalignant, anatomically complex, and symptomatic stenosis for which conventional stents were not suitable.
Disclosures: Dr. Guibert reported having no financial disclosures.
Source: Guibert N et al. ATS 2018, Abstract 4433.
AZD8871 delivered significant bronchodilation in two-week study
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
REPORTING FROM ATS 2018
Key clinical point: Once daily doses of AZD8871 100 mcg and 600 mcg elicited significant and clinically relevant differences in trough FEV1, compared with placebo.
Major finding: On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
Study details: A phase 2a trial of 42 patients aged 40-80 years with moderate to severe reversible COPD.
Disclosures: AstraZeneca sponsored the study. Dr. Singh reported financial affiliations with AstraZeneca and numerous other pharmaceutical companies.Source: Singh, D., et al. Abstract 7708, ATS 2018.
COPD patient subset gains no benefit from low-dose theophylline
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
AT ATS 2018
Key clinical point: Among COPD patients at high risk of exacerbation, adding low-dose oral theophylline to a drug regimen that includes an inhaled corticosteroid provides no overall clinical benefit.
Major finding: The number of exacerbations was 2.24 in participants allocated to theophylline and 2.23 for participants allocated to placebo.
Study details: A trial of 1,578 people with COPD and a history of at least two exacerbations in the previous year who were randomized to receive low-dose theophylline or placebo for one year.
Disclosures: The study was funded by National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
Source: Price, D., et al. Abstract 7709, ATS 2018.
Simple bedside tool effectively detected sepsis in the ED
SAN DIEGO – The product of compared with the quick Sequential Organ Failure Assessment prompt, a small, single-center study showed.
“We know a lot about the pathophysiology of sepsis, but we don’t have great ways of identifying septic patients at an early stage,” lead study author David Lynch, MD, said in an interview at an international conference of the American Thoracic Society.
He noted that screening tools such as the quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome criteria have a sensitivity of about 70% in detecting sepsis. “Over the last 10-15 years we’ve been able to find ways of improving outcomes in patients whom we confirm are septic with early antibiotics and fluids,” said Dr. Lynch, a second-year resident in the division of pulmonary and critical care medicine within the department of medicine at the University of North Carolina at Chapel Hill. “We know that in sepsis, systemic vascular resistance is decreased and cardiac output is increased. We tried to come up with a way of estimating cardiac output at the bedside by multiplying heart rate with pulse pressure, with the pulse pressure being the surrogate for stroke volume, which you can measure easily.”
In a cross-sectional, observational study, Dr. Lynch, senior author Thomas Bice, MD, and their associates reviewed the records of 116 patients who were admitted directly to the University of North Carolina’s medical ICU (MICU) from the UNC ED between Jan. 5, 2016, and June 30, 2017. The primary outcome of interest was culture-positive sepsis, and the primary exposure was the product of pulse pressure and heart rate. Patients were determined to be positive for sepsis if an infection was suspected (such as if blood cultures were drawn and antibiotics were started), the admitting physician suspected sepsis, and cultures were subsequently positive.
The average age of all patients was 53 years, 51% were female, the mortality rate was 12%, and the median length of stay was 4 days. A total of 25 of the 116 patients (22%) were positive for sepsis. The researchers observed that the pulse pressure multiplied by the heart rate was significantly higher in the culture-positive sepsis group, compared with controls (6,710 vs. 3,741, respectively; P less than .001).
Dr. Lynch and his associates found that, as a continuous variable, pulse pressure multiplied by the heart rate accurately classified 90% of sepsis cases (area under the receiver operator curve, 0.96; P less than .001). When using 5,000 as a cutoff, pulse pressure multiplied by the heart rate had a sensitivity of 100% and a specificity of 89% in detecting culture-positive sepsis. “We were surprised by how high the sensitivity was,” Dr. Lynch said. “The question is, will this translate to a larger cohort? And, would this be transferable to all patients in the ED, as opposed to the sicker patients who are going to the MICU?”
He and his associates plan to confirm the study’s results in a broader population of patients. “We don’t yet understand at what point in time this would be most applicable,” he added. “We looked at the first set of vitals when they came into the ED. We’d like to know if that applies to the second, third and fourth set of vitals, and whether it would be most useful to have an average of those.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Lynch reported having no financial disclosures.
SAN DIEGO – The product of compared with the quick Sequential Organ Failure Assessment prompt, a small, single-center study showed.
“We know a lot about the pathophysiology of sepsis, but we don’t have great ways of identifying septic patients at an early stage,” lead study author David Lynch, MD, said in an interview at an international conference of the American Thoracic Society.
He noted that screening tools such as the quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome criteria have a sensitivity of about 70% in detecting sepsis. “Over the last 10-15 years we’ve been able to find ways of improving outcomes in patients whom we confirm are septic with early antibiotics and fluids,” said Dr. Lynch, a second-year resident in the division of pulmonary and critical care medicine within the department of medicine at the University of North Carolina at Chapel Hill. “We know that in sepsis, systemic vascular resistance is decreased and cardiac output is increased. We tried to come up with a way of estimating cardiac output at the bedside by multiplying heart rate with pulse pressure, with the pulse pressure being the surrogate for stroke volume, which you can measure easily.”
In a cross-sectional, observational study, Dr. Lynch, senior author Thomas Bice, MD, and their associates reviewed the records of 116 patients who were admitted directly to the University of North Carolina’s medical ICU (MICU) from the UNC ED between Jan. 5, 2016, and June 30, 2017. The primary outcome of interest was culture-positive sepsis, and the primary exposure was the product of pulse pressure and heart rate. Patients were determined to be positive for sepsis if an infection was suspected (such as if blood cultures were drawn and antibiotics were started), the admitting physician suspected sepsis, and cultures were subsequently positive.
The average age of all patients was 53 years, 51% were female, the mortality rate was 12%, and the median length of stay was 4 days. A total of 25 of the 116 patients (22%) were positive for sepsis. The researchers observed that the pulse pressure multiplied by the heart rate was significantly higher in the culture-positive sepsis group, compared with controls (6,710 vs. 3,741, respectively; P less than .001).
Dr. Lynch and his associates found that, as a continuous variable, pulse pressure multiplied by the heart rate accurately classified 90% of sepsis cases (area under the receiver operator curve, 0.96; P less than .001). When using 5,000 as a cutoff, pulse pressure multiplied by the heart rate had a sensitivity of 100% and a specificity of 89% in detecting culture-positive sepsis. “We were surprised by how high the sensitivity was,” Dr. Lynch said. “The question is, will this translate to a larger cohort? And, would this be transferable to all patients in the ED, as opposed to the sicker patients who are going to the MICU?”
He and his associates plan to confirm the study’s results in a broader population of patients. “We don’t yet understand at what point in time this would be most applicable,” he added. “We looked at the first set of vitals when they came into the ED. We’d like to know if that applies to the second, third and fourth set of vitals, and whether it would be most useful to have an average of those.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Lynch reported having no financial disclosures.
SAN DIEGO – The product of compared with the quick Sequential Organ Failure Assessment prompt, a small, single-center study showed.
“We know a lot about the pathophysiology of sepsis, but we don’t have great ways of identifying septic patients at an early stage,” lead study author David Lynch, MD, said in an interview at an international conference of the American Thoracic Society.
He noted that screening tools such as the quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome criteria have a sensitivity of about 70% in detecting sepsis. “Over the last 10-15 years we’ve been able to find ways of improving outcomes in patients whom we confirm are septic with early antibiotics and fluids,” said Dr. Lynch, a second-year resident in the division of pulmonary and critical care medicine within the department of medicine at the University of North Carolina at Chapel Hill. “We know that in sepsis, systemic vascular resistance is decreased and cardiac output is increased. We tried to come up with a way of estimating cardiac output at the bedside by multiplying heart rate with pulse pressure, with the pulse pressure being the surrogate for stroke volume, which you can measure easily.”
In a cross-sectional, observational study, Dr. Lynch, senior author Thomas Bice, MD, and their associates reviewed the records of 116 patients who were admitted directly to the University of North Carolina’s medical ICU (MICU) from the UNC ED between Jan. 5, 2016, and June 30, 2017. The primary outcome of interest was culture-positive sepsis, and the primary exposure was the product of pulse pressure and heart rate. Patients were determined to be positive for sepsis if an infection was suspected (such as if blood cultures were drawn and antibiotics were started), the admitting physician suspected sepsis, and cultures were subsequently positive.
The average age of all patients was 53 years, 51% were female, the mortality rate was 12%, and the median length of stay was 4 days. A total of 25 of the 116 patients (22%) were positive for sepsis. The researchers observed that the pulse pressure multiplied by the heart rate was significantly higher in the culture-positive sepsis group, compared with controls (6,710 vs. 3,741, respectively; P less than .001).
Dr. Lynch and his associates found that, as a continuous variable, pulse pressure multiplied by the heart rate accurately classified 90% of sepsis cases (area under the receiver operator curve, 0.96; P less than .001). When using 5,000 as a cutoff, pulse pressure multiplied by the heart rate had a sensitivity of 100% and a specificity of 89% in detecting culture-positive sepsis. “We were surprised by how high the sensitivity was,” Dr. Lynch said. “The question is, will this translate to a larger cohort? And, would this be transferable to all patients in the ED, as opposed to the sicker patients who are going to the MICU?”
He and his associates plan to confirm the study’s results in a broader population of patients. “We don’t yet understand at what point in time this would be most applicable,” he added. “We looked at the first set of vitals when they came into the ED. We’d like to know if that applies to the second, third and fourth set of vitals, and whether it would be most useful to have an average of those.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Lynch reported having no financial disclosures.
REPORTING FROM ATS 2018
Key clinical point: A simple calculation of pulse pressure multiplied by heart rate at ED triage could lead to earlier implementation of lifesaving interventions in septic patients.
Major finding: When using 5,000 as a cutoff, pulse pressure multiplied by heart rate had a sensitivity of 100% and a specificity of 89% in detecting culture-positive sepsis.
Study details: A cross-sectional, observational study of 116 medical ICU patients who were admitted directly from an ED.
Disclosures: The study was supported in part by a grant from the National Institutes of Health. Dr. Lynch reported having no financial disclosures.
In-hospital mortality predictors eyed in pneumonia patient subset
SAN DIEGO –, results from a large retrospective cohort study found.
In a poster abstract presented at an international conference of the American Thoracic Society, researchers led by Thomas P. Lodise Jr., PharmD, noted that ventilator-associated pneumonia is one of the most common hospital-acquired infections in intensive care units and affected an estimated 9%-27% of all intubated patients. “While data are readily available surrounding mortality associated with VAP, scant data are available on outcomes associated with any type of pneumonia requiring intubation and mechanical ventilation (MV) caused by gram-negative organisms,” they wrote.
In an effort to describe mortality rates and associated risk factors for intubated and MV patients diagnosed with gram-negative pneumonia, Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences and his associates conducted a retrospective cohort study of data from the Healthcare Cost and Utilization Project (HCUP) National Readmission Database (NRD). HCUP is the largest source of hospital care data in the United States, accounting for 49.3% of the total U.S. resident population and 49.1% of U.S. hospitalizations. The researchers included patients at least 18 years of age who were hospitalized with a primary or secondary diagnosis of gram-negative pneumonia between Feb. 1, 2013, and Nov. 30, 2013. They excluded index hospitalizations with a primary or secondary diagnosis of viral pneumonia, fungal pneumonia, atypical organisms, gram-positive bacterial pneumonia, or pneumonia occurring secondary to an infectious disease. They examined mortality rates descriptively and modeled them via adjusted multivariate logistic regression to evaluate the impact of baseline characteristics and comorbidities on risk of mortality. All analyses incorporated sample weights to increase generalizability and allow for extrapolation to the entire U.S. population.
A total of 32,683 patients met all study criteria. Of these, 2,323 (7.1%) had a primary diagnosis and 30,360 (92.9%) had a secondary diagnosis for gram-negative pneumonia. Their mean age was 64 years, and 61.1% were male. In all, 7,928 patients (24.3%) died during hospitalization. Multivariate analysis revealed that patients with concomitant sepsis had the highest risk of mortality (odds ratio, 2.60), followed by patients aged 65 years and older (OR, 1.88) and those with any prior hospitalization within 30 days (OR, 1.34). Comorbidities upon admission with highest risk of mortality included cancer (OR, 2.45), liver disease (OR, 1.91), AIDS/HIV (OR, 1.59), renal disease (OR, 1.33), and congestive heart failure (OR, 1.15). Diabetes was found to have a decreased risk of mortality, with an OR of 0.80. “However, a majority of patients with diabetes had no complications; thus, these patients may be representative of a less severe patient population,” Dr. Lodise and his associates noted in the poster.
They acknowledged certain limitations of the study, including the potential for coding errors. They also pointed out the HCUP NRD does not contain treatment-specific information, drugs administered or treatment patterns during hospitalization, the number of days patients spent in the ICU, or the number of days on ventilation, “which can influence outcomes in pneumonia patients.” In addition, the study did not attempt to determine cause of death. “Death may have been due to combinations of factors separate from pneumonia,” they wrote.
Bayer Healthcare Pharmaceuticals funded the study. Dr. Lodise reported having no financial disclosures.
[email protected]
SOURCE: Lodise T. et al. ATS 2018, Poster 272.
SAN DIEGO –, results from a large retrospective cohort study found.
In a poster abstract presented at an international conference of the American Thoracic Society, researchers led by Thomas P. Lodise Jr., PharmD, noted that ventilator-associated pneumonia is one of the most common hospital-acquired infections in intensive care units and affected an estimated 9%-27% of all intubated patients. “While data are readily available surrounding mortality associated with VAP, scant data are available on outcomes associated with any type of pneumonia requiring intubation and mechanical ventilation (MV) caused by gram-negative organisms,” they wrote.
In an effort to describe mortality rates and associated risk factors for intubated and MV patients diagnosed with gram-negative pneumonia, Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences and his associates conducted a retrospective cohort study of data from the Healthcare Cost and Utilization Project (HCUP) National Readmission Database (NRD). HCUP is the largest source of hospital care data in the United States, accounting for 49.3% of the total U.S. resident population and 49.1% of U.S. hospitalizations. The researchers included patients at least 18 years of age who were hospitalized with a primary or secondary diagnosis of gram-negative pneumonia between Feb. 1, 2013, and Nov. 30, 2013. They excluded index hospitalizations with a primary or secondary diagnosis of viral pneumonia, fungal pneumonia, atypical organisms, gram-positive bacterial pneumonia, or pneumonia occurring secondary to an infectious disease. They examined mortality rates descriptively and modeled them via adjusted multivariate logistic regression to evaluate the impact of baseline characteristics and comorbidities on risk of mortality. All analyses incorporated sample weights to increase generalizability and allow for extrapolation to the entire U.S. population.
A total of 32,683 patients met all study criteria. Of these, 2,323 (7.1%) had a primary diagnosis and 30,360 (92.9%) had a secondary diagnosis for gram-negative pneumonia. Their mean age was 64 years, and 61.1% were male. In all, 7,928 patients (24.3%) died during hospitalization. Multivariate analysis revealed that patients with concomitant sepsis had the highest risk of mortality (odds ratio, 2.60), followed by patients aged 65 years and older (OR, 1.88) and those with any prior hospitalization within 30 days (OR, 1.34). Comorbidities upon admission with highest risk of mortality included cancer (OR, 2.45), liver disease (OR, 1.91), AIDS/HIV (OR, 1.59), renal disease (OR, 1.33), and congestive heart failure (OR, 1.15). Diabetes was found to have a decreased risk of mortality, with an OR of 0.80. “However, a majority of patients with diabetes had no complications; thus, these patients may be representative of a less severe patient population,” Dr. Lodise and his associates noted in the poster.
They acknowledged certain limitations of the study, including the potential for coding errors. They also pointed out the HCUP NRD does not contain treatment-specific information, drugs administered or treatment patterns during hospitalization, the number of days patients spent in the ICU, or the number of days on ventilation, “which can influence outcomes in pneumonia patients.” In addition, the study did not attempt to determine cause of death. “Death may have been due to combinations of factors separate from pneumonia,” they wrote.
Bayer Healthcare Pharmaceuticals funded the study. Dr. Lodise reported having no financial disclosures.
[email protected]
SOURCE: Lodise T. et al. ATS 2018, Poster 272.
SAN DIEGO –, results from a large retrospective cohort study found.
In a poster abstract presented at an international conference of the American Thoracic Society, researchers led by Thomas P. Lodise Jr., PharmD, noted that ventilator-associated pneumonia is one of the most common hospital-acquired infections in intensive care units and affected an estimated 9%-27% of all intubated patients. “While data are readily available surrounding mortality associated with VAP, scant data are available on outcomes associated with any type of pneumonia requiring intubation and mechanical ventilation (MV) caused by gram-negative organisms,” they wrote.
In an effort to describe mortality rates and associated risk factors for intubated and MV patients diagnosed with gram-negative pneumonia, Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences and his associates conducted a retrospective cohort study of data from the Healthcare Cost and Utilization Project (HCUP) National Readmission Database (NRD). HCUP is the largest source of hospital care data in the United States, accounting for 49.3% of the total U.S. resident population and 49.1% of U.S. hospitalizations. The researchers included patients at least 18 years of age who were hospitalized with a primary or secondary diagnosis of gram-negative pneumonia between Feb. 1, 2013, and Nov. 30, 2013. They excluded index hospitalizations with a primary or secondary diagnosis of viral pneumonia, fungal pneumonia, atypical organisms, gram-positive bacterial pneumonia, or pneumonia occurring secondary to an infectious disease. They examined mortality rates descriptively and modeled them via adjusted multivariate logistic regression to evaluate the impact of baseline characteristics and comorbidities on risk of mortality. All analyses incorporated sample weights to increase generalizability and allow for extrapolation to the entire U.S. population.
A total of 32,683 patients met all study criteria. Of these, 2,323 (7.1%) had a primary diagnosis and 30,360 (92.9%) had a secondary diagnosis for gram-negative pneumonia. Their mean age was 64 years, and 61.1% were male. In all, 7,928 patients (24.3%) died during hospitalization. Multivariate analysis revealed that patients with concomitant sepsis had the highest risk of mortality (odds ratio, 2.60), followed by patients aged 65 years and older (OR, 1.88) and those with any prior hospitalization within 30 days (OR, 1.34). Comorbidities upon admission with highest risk of mortality included cancer (OR, 2.45), liver disease (OR, 1.91), AIDS/HIV (OR, 1.59), renal disease (OR, 1.33), and congestive heart failure (OR, 1.15). Diabetes was found to have a decreased risk of mortality, with an OR of 0.80. “However, a majority of patients with diabetes had no complications; thus, these patients may be representative of a less severe patient population,” Dr. Lodise and his associates noted in the poster.
They acknowledged certain limitations of the study, including the potential for coding errors. They also pointed out the HCUP NRD does not contain treatment-specific information, drugs administered or treatment patterns during hospitalization, the number of days patients spent in the ICU, or the number of days on ventilation, “which can influence outcomes in pneumonia patients.” In addition, the study did not attempt to determine cause of death. “Death may have been due to combinations of factors separate from pneumonia,” they wrote.
Bayer Healthcare Pharmaceuticals funded the study. Dr. Lodise reported having no financial disclosures.
[email protected]
SOURCE: Lodise T. et al. ATS 2018, Poster 272.
AT ATS 2018
Key clinical point: Before this analysis, mortality and associated risk factors for intubated or mechanically ventilated patients diagnosed with gram-negative pneumonia were poorly understood.
Major finding: Among hospitalized, intubated or mechanically ventilated patients with gram-negative pneumonia, 24.3% died during their hospital stay.
Study details: A retrospective cohort study of data from 32,683 patients who were hospitalized with a primary or secondary diagnosis of gram-negative pneumonia.
Disclosures: Bayer Healthcare Pharmaceuticals funded the study. Dr. Lodise reported having no financial disclosures.
Source: Lodise T. et al. ATS 2018, Poster 272.