COPD

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.

[email protected]

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.

[email protected]

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.

[email protected]

SOURCE: Schneeberger T et al. ATS 2018, Abstract A2453.


 

SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States 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.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States 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.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States 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.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

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 COPD with significant cardiovascular risk factors, 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 COPD with significant cardiovascular risk factors, 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 COPD with significant cardiovascular risk factors, 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.

A brief patient-directed education program delivered at the time of hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) improved disease-specific knowledge, according to results of a pilot randomized trial.

Patients who participated in education sessions had a significant improvement in their scores on the Bristol COPD Knowledge Questionnaire (BCKQ), compared with control patients who received no education, study investigators reported in the journal Chest.

“Early education may be a bridge to more active approaches and could provide an important contribution to self-management interventions post-AECOPD,” wrote first author Tania Janaudis-Ferreira, PhD, of the School of Physical and Occupational Therapy, McGill University, Montreal, and her co-authors.

In the study, patients admitted to a community hospital with an AECOPD were randomized to standard care plus brief education or standard care alone. The education consisted of two 30-minute sessions delivered by a physiotherapist, either in the hospital or at home up to 2 weeks after the admission.

Before and after the intervention period, participant knowledge was measured using both the BCKQ and the Lung Information Needs Questionnaire (LINQ).

A total of 31 patients participated, including 15 in the intervention group and 16 in the control group, although 3 patients in the control group did not complete the follow-up testing, investigators said in their report.

The mean change in BCKQ was 8 points for the educational intervention group, and 3.4 for the control group (P = 0.02). That result was in keeping with findings of a previous randomized study noting an 8.3-point change in BCKQ scores for COPD patients who received education in the primary care setting, Dr. Janaudis-Ferreira and co-authors said.

“The change itself is relatively modest, suggesting more frequent sessions might result in greater improvements,” they wrote. For example, they said, an 8-week educational intervention delivered in the context of pulmonary rehabilitation program in one study yielded a mean change of 18.3 points on the BCKQ in the intervention group.

By contrast, the investigators found no significant difference in LINQ score changes between the intervention and control groups (P = .8).

That may indicate that two 30-minute sessions were not sufficient to attend to patients’ learning needs, authors said, though it could also have been an issue with the instrument itself in the setting of this study.

“The majority of the questions in the LINQ ask whether or not a doctor or nurse has explained a specific question to the patient,” authors explained. “Since a physiotherapist delivered the program, had the wording been altered to include physiotherapists or a more general term for healthcare professionals, we may have seen a change in these results.”

Dr. Janaudis-Ferreira and co-authors had no conflicts of interest to disclose. The study was funded by a grant from the Canadian Respiratory Health Professionals, which did not have input in research or manuscript development.

SOURCE: Janaudis-Ferreira T, et al.  Chest
 

A brief patient-directed education program delivered at the time of hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) improved disease-specific knowledge, according to results of a pilot randomized trial.

Patients who participated in education sessions had a significant improvement in their scores on the Bristol COPD Knowledge Questionnaire (BCKQ), compared with control patients who received no education, study investigators reported in the journal Chest.

“Early education may be a bridge to more active approaches and could provide an important contribution to self-management interventions post-AECOPD,” wrote first author Tania Janaudis-Ferreira, PhD, of the School of Physical and Occupational Therapy, McGill University, Montreal, and her co-authors.

In the study, patients admitted to a community hospital with an AECOPD were randomized to standard care plus brief education or standard care alone. The education consisted of two 30-minute sessions delivered by a physiotherapist, either in the hospital or at home up to 2 weeks after the admission.

Before and after the intervention period, participant knowledge was measured using both the BCKQ and the Lung Information Needs Questionnaire (LINQ).

A total of 31 patients participated, including 15 in the intervention group and 16 in the control group, although 3 patients in the control group did not complete the follow-up testing, investigators said in their report.

The mean change in BCKQ was 8 points for the educational intervention group, and 3.4 for the control group (P = 0.02). That result was in keeping with findings of a previous randomized study noting an 8.3-point change in BCKQ scores for COPD patients who received education in the primary care setting, Dr. Janaudis-Ferreira and co-authors said.

“The change itself is relatively modest, suggesting more frequent sessions might result in greater improvements,” they wrote. For example, they said, an 8-week educational intervention delivered in the context of pulmonary rehabilitation program in one study yielded a mean change of 18.3 points on the BCKQ in the intervention group.

By contrast, the investigators found no significant difference in LINQ score changes between the intervention and control groups (P = .8).

That may indicate that two 30-minute sessions were not sufficient to attend to patients’ learning needs, authors said, though it could also have been an issue with the instrument itself in the setting of this study.

“The majority of the questions in the LINQ ask whether or not a doctor or nurse has explained a specific question to the patient,” authors explained. “Since a physiotherapist delivered the program, had the wording been altered to include physiotherapists or a more general term for healthcare professionals, we may have seen a change in these results.”

Dr. Janaudis-Ferreira and co-authors had no conflicts of interest to disclose. The study was funded by a grant from the Canadian Respiratory Health Professionals, which did not have input in research or manuscript development.

SOURCE: Janaudis-Ferreira T, et al.  Chest
 

A brief patient-directed education program delivered at the time of hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) improved disease-specific knowledge, according to results of a pilot randomized trial.

Patients who participated in education sessions had a significant improvement in their scores on the Bristol COPD Knowledge Questionnaire (BCKQ), compared with control patients who received no education, study investigators reported in the journal Chest.

“Early education may be a bridge to more active approaches and could provide an important contribution to self-management interventions post-AECOPD,” wrote first author Tania Janaudis-Ferreira, PhD, of the School of Physical and Occupational Therapy, McGill University, Montreal, and her co-authors.

In the study, patients admitted to a community hospital with an AECOPD were randomized to standard care plus brief education or standard care alone. The education consisted of two 30-minute sessions delivered by a physiotherapist, either in the hospital or at home up to 2 weeks after the admission.

Before and after the intervention period, participant knowledge was measured using both the BCKQ and the Lung Information Needs Questionnaire (LINQ).

A total of 31 patients participated, including 15 in the intervention group and 16 in the control group, although 3 patients in the control group did not complete the follow-up testing, investigators said in their report.

The mean change in BCKQ was 8 points for the educational intervention group, and 3.4 for the control group (P = 0.02). That result was in keeping with findings of a previous randomized study noting an 8.3-point change in BCKQ scores for COPD patients who received education in the primary care setting, Dr. Janaudis-Ferreira and co-authors said.

“The change itself is relatively modest, suggesting more frequent sessions might result in greater improvements,” they wrote. For example, they said, an 8-week educational intervention delivered in the context of pulmonary rehabilitation program in one study yielded a mean change of 18.3 points on the BCKQ in the intervention group.

By contrast, the investigators found no significant difference in LINQ score changes between the intervention and control groups (P = .8).

That may indicate that two 30-minute sessions were not sufficient to attend to patients’ learning needs, authors said, though it could also have been an issue with the instrument itself in the setting of this study.

“The majority of the questions in the LINQ ask whether or not a doctor or nurse has explained a specific question to the patient,” authors explained. “Since a physiotherapist delivered the program, had the wording been altered to include physiotherapists or a more general term for healthcare professionals, we may have seen a change in these results.”

Dr. Janaudis-Ferreira and co-authors had no conflicts of interest to disclose. The study was funded by a grant from the Canadian Respiratory Health Professionals, which did not have input in research or manuscript development.

SOURCE: Janaudis-Ferreira T, et al.  Chest
 

SAN DIEGO – The investigational agent AZD8871 at once daily doses of 100 mcg and 600 mcg led to statistically significant, clinically relevant, and dose-ordered differences in trough FEV₁ at two weeks compared with placebo, 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.”

Doug Brunk/MDedge News

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 FEV_1, 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.

[email protected]

SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.

SAN DIEGO – The investigational agent AZD8871 at once daily doses of 100 mcg and 600 mcg led to statistically significant, clinically relevant, and dose-ordered differences in trough FEV₁ at two weeks compared with placebo, 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.”

Doug Brunk/MDedge News

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 FEV_1, 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.

[email protected]

SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.

SAN DIEGO – The investigational agent AZD8871 at once daily doses of 100 mcg and 600 mcg led to statistically significant, clinically relevant, and dose-ordered differences in trough FEV₁ at two weeks compared with placebo, 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.”

Doug Brunk/MDedge News

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 FEV_1, 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.

[email protected]

SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“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.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“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.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“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.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.

Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.

SOURCE: Chapman K et al. ATS 2018 Abstract A1009.

SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.

Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.

SOURCE: Chapman K et al. ATS 2018 Abstract A1009.

SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.

Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.

SOURCE: Chapman K et al. ATS 2018 Abstract A1009.

CHEST^® Physician’s coverage of the American Thoracic Society International Conference at the San Diego Convention Center begins on May 20. Here is a glimpse of some of the important research that will be presented at this meeting.

The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta₂-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.

One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.

At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.

On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”

Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.

[email protected]

CHEST^® Physician’s coverage of the American Thoracic Society International Conference at the San Diego Convention Center begins on May 20. Here is a glimpse of some of the important research that will be presented at this meeting.

The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta₂-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.

One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.

At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.

On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”

Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.

[email protected]

CHEST^® Physician’s coverage of the American Thoracic Society International Conference at the San Diego Convention Center begins on May 20. Here is a glimpse of some of the important research that will be presented at this meeting.

The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta₂-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.

One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.

At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.

On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”

Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.

[email protected]

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

Tai chi appears to be an appropriate substitute for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) and seems to confer better long-term improvement, suggests a study published online in the journal CHEST^®.

Willie B. Thomas/iStockphoto

[email protected]

SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.

Tai chi appears to be an appropriate substitute for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) and seems to confer better long-term improvement, suggests a study published online in the journal CHEST^®.

Willie B. Thomas/iStockphoto

[email protected]

SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.

Tai chi appears to be an appropriate substitute for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) and seems to confer better long-term improvement, suggests a study published online in the journal CHEST^®.

Willie B. Thomas/iStockphoto

[email protected]

SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.