American College of Chest Physicians (ACCP): Annual International Scientific Assembly (CHEST 2012)

ATLANTA – A Kansas-based program that aims to improve sepsis-related outcomes in rural hospital settings is proving successful and could serve as a model for rural hospitals nationwide.

The program, known as "The Kansas Sepsis Project," was initiated by the Midwest Critical Care Collaborative, and focuses on a simplified approach to sepsis resuscitation for the purpose of reducing sepsis mortality, Dr. Steven Q. Simpson reported at the annual meeting of the American College of Chest Physicians.

Sepsis affects more than 10,000 Kansans each year, and the sepsis-related mortality rate is 30%-50% in most Kansas hospitals, which exceeds the mortality rate associated with acute myocardial infarction, said Dr. Simpson of the University of Kansas Medical Center, Kansas City.

One goal of the sepsis project is to reduce that rate by 10% by the end of 2015.

According to the Midwest Critical Care Collaborative website, a 20% reduction is possible if specific plans for recognition and treatment as outlined by the project are put in place.

The project, which is open to any interested facility including those not based in Kansas, involves baseline surveys, live and online training, ongoing data collection and analysis, formation of performance improvement planning based on those analyses, and – hopefully – changed behavior and reduced sepsis mortality, said Dr. Simpson.

The website states that participants learn to:

• Recognize cardinal features of severe sepsis.

• Initiate rapid, organized care for severe sepsis.

• Evaluate in-house data for recognizing and caring for severe sepsis patients.

• Initiate a performance improvement program, and improve outcomes for patients with severe sepsis.

Participants also have access to useful Web-based tools, such as a severe sepsis screener and a severe sepsis tracker for small hospitals, both of which help to ensure that proper protocols are followed, and that data are tracked.

A severe sepsis protocol for emergency management in small, referring hospitals states that whenever possible, nine steps should be completed within 2 hours for patients with infection, systemic inflammatory response syndrome, and dysfunction of one or more organs. The steps are, if possible:

• Draw blood for serum lactate measurement.

• Draw two sets of blood cultures – before antibiotics are initiated, if possible; however, do not delay antibiotics for the sake of completing this step.

• Start two peripheral intravenous lines (use 18 gauge or larger).

• Initiate broad-spectrum antibiotics as soon as possible.

• Give 2 L of normal saline solution or lactated Ringer’s solution, wide open.

• Draw blood for a complete blood count with a differential, basic chemistry panel if this has not already been done.

• Administer supplemental oxygen to maintain oxygen saturation measured by pulse oximeter above 90%.

• Initiate norepinephrine or dopamine if shock is present. This maintains a mean arterial pressure of 65 mm Hg or greater. Continue intravenous crystalloid at 250 mL/hr.

• Transfer the patient if serum lactate is 4 mmol/L or greater, if systolic blood pressure remains below 90 mm Hg, or if mean arterial pressure is less than 60 mm Hg after 2 L of crystalloid. Place a central venous catheter only if this can be accomplished without delaying transfer.

Following this protocol and using the tools available through the project is leading to dramatic improvements in outcomes. At one hospital, for example, a review of 67 charts from 2009 and 2010 revealed that of 28 cases that met criteria for sepsis, none was identified as such.

Since the hospital entered the project, an additional 61 patients screened positive. Of those, 59 had the severe sepsis tracker completed, 56 had blood cultures drawn prior to administration of broad-spectrum antibiotics, and 57 received broad-spectrum antibiotics within 1 hour of presentation.

Additionally, 22 of the 59 patients for whom the severe sepsis tracker was completed had hypotension, and 18 of those received a 20-mL/kg fluid bolus within 2 hours of diagnosis.

Overall, 54 of the 59 patients who had the severe sepsis tracker completed survived their hospitalization. Only 2 of 35 patients with severe sepsis (5.7%) required transfer to a larger facility because of deterioration in their condition, compared with 7 of 28 patients (25%) in the group from the 2009-2010 preproject chart review.

Numerous states across the United States, especially in the Midwest and Northwest, have rural populations of less than 86 per square mile, similar to Kansas, with 1.330 small facilities serving rural populations located many miles from the nearest referral hospital, and could benefit from this approach to sepsis resuscitation, Dr. Simpson said.

The need for attention to the problem of sepsis is apparent not only based on the high mortality rates, but also in the outcomes of focus group research showing that only 42% of responding physicians from rural settings consider themselves to be "very knowledgeable" about sepsis diagnosis, treatments, and complications; while the same percentage consider themselves "not too knowledgeable," 4% say they are not at all knowledgeable, and 12% say they aren’t sure how knowledgeable they are, he said.

Similarly, only 2% of respondents said they are extremely knowledgeable about the differences among uncomplicated sepsis, severe sepsis, and septic shock; 27% said they are very knowledgeable; 61% said they are not too knowledgeable; 4% said they are not at all knowledgeable; and 6% said they are unsure how knowledgeable they are.

Few respondents were familiar with the Early Goal-Directed Therapy protocol or the Surviving Sepsis Campaign, and most admitted that the likelihood of missed sepsis diagnoses is high at their institution.

Most (about 85%) agreed that additional training would be extremely beneficial.

Although several challenges and hurdles exist with respect to improving sepsis outcomes in rural settings, including staffing issues, the lack of recognition of the extent of the problem, and the fact that sepsis is not yet a Joint Commission core measure, the results thus far of the Kansas Sepsis Project suggest positive change is within reach, Dr. Simpson said.

For more information about the project, click here.

The Kansas Sepsis Project is supported by the One Breath Foundation in the form of the Third Eli Lilly Distinguished Scholar in Critical Care Medicine Award. Dr. Simpson reported having no relevant financial disclosures.

ATLANTA – A Kansas-based program that aims to improve sepsis-related outcomes in rural hospital settings is proving successful and could serve as a model for rural hospitals nationwide.

The program, known as "The Kansas Sepsis Project," was initiated by the Midwest Critical Care Collaborative, and focuses on a simplified approach to sepsis resuscitation for the purpose of reducing sepsis mortality, Dr. Steven Q. Simpson reported at the annual meeting of the American College of Chest Physicians.

Sepsis affects more than 10,000 Kansans each year, and the sepsis-related mortality rate is 30%-50% in most Kansas hospitals, which exceeds the mortality rate associated with acute myocardial infarction, said Dr. Simpson of the University of Kansas Medical Center, Kansas City.

One goal of the sepsis project is to reduce that rate by 10% by the end of 2015.

According to the Midwest Critical Care Collaborative website, a 20% reduction is possible if specific plans for recognition and treatment as outlined by the project are put in place.

The project, which is open to any interested facility including those not based in Kansas, involves baseline surveys, live and online training, ongoing data collection and analysis, formation of performance improvement planning based on those analyses, and – hopefully – changed behavior and reduced sepsis mortality, said Dr. Simpson.

The website states that participants learn to:

• Recognize cardinal features of severe sepsis.

• Initiate rapid, organized care for severe sepsis.

• Evaluate in-house data for recognizing and caring for severe sepsis patients.

• Initiate a performance improvement program, and improve outcomes for patients with severe sepsis.

Participants also have access to useful Web-based tools, such as a severe sepsis screener and a severe sepsis tracker for small hospitals, both of which help to ensure that proper protocols are followed, and that data are tracked.

A severe sepsis protocol for emergency management in small, referring hospitals states that whenever possible, nine steps should be completed within 2 hours for patients with infection, systemic inflammatory response syndrome, and dysfunction of one or more organs. The steps are, if possible:

• Draw blood for serum lactate measurement.

• Draw two sets of blood cultures – before antibiotics are initiated, if possible; however, do not delay antibiotics for the sake of completing this step.

• Start two peripheral intravenous lines (use 18 gauge or larger).

• Initiate broad-spectrum antibiotics as soon as possible.

• Give 2 L of normal saline solution or lactated Ringer’s solution, wide open.

• Draw blood for a complete blood count with a differential, basic chemistry panel if this has not already been done.

• Administer supplemental oxygen to maintain oxygen saturation measured by pulse oximeter above 90%.

• Initiate norepinephrine or dopamine if shock is present. This maintains a mean arterial pressure of 65 mm Hg or greater. Continue intravenous crystalloid at 250 mL/hr.

• Transfer the patient if serum lactate is 4 mmol/L or greater, if systolic blood pressure remains below 90 mm Hg, or if mean arterial pressure is less than 60 mm Hg after 2 L of crystalloid. Place a central venous catheter only if this can be accomplished without delaying transfer.

Following this protocol and using the tools available through the project is leading to dramatic improvements in outcomes. At one hospital, for example, a review of 67 charts from 2009 and 2010 revealed that of 28 cases that met criteria for sepsis, none was identified as such.

Since the hospital entered the project, an additional 61 patients screened positive. Of those, 59 had the severe sepsis tracker completed, 56 had blood cultures drawn prior to administration of broad-spectrum antibiotics, and 57 received broad-spectrum antibiotics within 1 hour of presentation.

Additionally, 22 of the 59 patients for whom the severe sepsis tracker was completed had hypotension, and 18 of those received a 20-mL/kg fluid bolus within 2 hours of diagnosis.

Overall, 54 of the 59 patients who had the severe sepsis tracker completed survived their hospitalization. Only 2 of 35 patients with severe sepsis (5.7%) required transfer to a larger facility because of deterioration in their condition, compared with 7 of 28 patients (25%) in the group from the 2009-2010 preproject chart review.

Numerous states across the United States, especially in the Midwest and Northwest, have rural populations of less than 86 per square mile, similar to Kansas, with 1.330 small facilities serving rural populations located many miles from the nearest referral hospital, and could benefit from this approach to sepsis resuscitation, Dr. Simpson said.

The need for attention to the problem of sepsis is apparent not only based on the high mortality rates, but also in the outcomes of focus group research showing that only 42% of responding physicians from rural settings consider themselves to be "very knowledgeable" about sepsis diagnosis, treatments, and complications; while the same percentage consider themselves "not too knowledgeable," 4% say they are not at all knowledgeable, and 12% say they aren’t sure how knowledgeable they are, he said.

Similarly, only 2% of respondents said they are extremely knowledgeable about the differences among uncomplicated sepsis, severe sepsis, and septic shock; 27% said they are very knowledgeable; 61% said they are not too knowledgeable; 4% said they are not at all knowledgeable; and 6% said they are unsure how knowledgeable they are.

Few respondents were familiar with the Early Goal-Directed Therapy protocol or the Surviving Sepsis Campaign, and most admitted that the likelihood of missed sepsis diagnoses is high at their institution.

Most (about 85%) agreed that additional training would be extremely beneficial.

Although several challenges and hurdles exist with respect to improving sepsis outcomes in rural settings, including staffing issues, the lack of recognition of the extent of the problem, and the fact that sepsis is not yet a Joint Commission core measure, the results thus far of the Kansas Sepsis Project suggest positive change is within reach, Dr. Simpson said.

For more information about the project, click here.

The Kansas Sepsis Project is supported by the One Breath Foundation in the form of the Third Eli Lilly Distinguished Scholar in Critical Care Medicine Award. Dr. Simpson reported having no relevant financial disclosures.

ATLANTA – A Kansas-based program that aims to improve sepsis-related outcomes in rural hospital settings is proving successful and could serve as a model for rural hospitals nationwide.

The program, known as "The Kansas Sepsis Project," was initiated by the Midwest Critical Care Collaborative, and focuses on a simplified approach to sepsis resuscitation for the purpose of reducing sepsis mortality, Dr. Steven Q. Simpson reported at the annual meeting of the American College of Chest Physicians.

Sepsis affects more than 10,000 Kansans each year, and the sepsis-related mortality rate is 30%-50% in most Kansas hospitals, which exceeds the mortality rate associated with acute myocardial infarction, said Dr. Simpson of the University of Kansas Medical Center, Kansas City.

One goal of the sepsis project is to reduce that rate by 10% by the end of 2015.

According to the Midwest Critical Care Collaborative website, a 20% reduction is possible if specific plans for recognition and treatment as outlined by the project are put in place.

The project, which is open to any interested facility including those not based in Kansas, involves baseline surveys, live and online training, ongoing data collection and analysis, formation of performance improvement planning based on those analyses, and – hopefully – changed behavior and reduced sepsis mortality, said Dr. Simpson.

The website states that participants learn to:

• Recognize cardinal features of severe sepsis.

• Initiate rapid, organized care for severe sepsis.

• Evaluate in-house data for recognizing and caring for severe sepsis patients.

• Initiate a performance improvement program, and improve outcomes for patients with severe sepsis.

Participants also have access to useful Web-based tools, such as a severe sepsis screener and a severe sepsis tracker for small hospitals, both of which help to ensure that proper protocols are followed, and that data are tracked.

A severe sepsis protocol for emergency management in small, referring hospitals states that whenever possible, nine steps should be completed within 2 hours for patients with infection, systemic inflammatory response syndrome, and dysfunction of one or more organs. The steps are, if possible:

• Draw blood for serum lactate measurement.

• Draw two sets of blood cultures – before antibiotics are initiated, if possible; however, do not delay antibiotics for the sake of completing this step.

• Start two peripheral intravenous lines (use 18 gauge or larger).

• Initiate broad-spectrum antibiotics as soon as possible.

• Give 2 L of normal saline solution or lactated Ringer’s solution, wide open.

• Draw blood for a complete blood count with a differential, basic chemistry panel if this has not already been done.

• Administer supplemental oxygen to maintain oxygen saturation measured by pulse oximeter above 90%.

• Initiate norepinephrine or dopamine if shock is present. This maintains a mean arterial pressure of 65 mm Hg or greater. Continue intravenous crystalloid at 250 mL/hr.

• Transfer the patient if serum lactate is 4 mmol/L or greater, if systolic blood pressure remains below 90 mm Hg, or if mean arterial pressure is less than 60 mm Hg after 2 L of crystalloid. Place a central venous catheter only if this can be accomplished without delaying transfer.

Following this protocol and using the tools available through the project is leading to dramatic improvements in outcomes. At one hospital, for example, a review of 67 charts from 2009 and 2010 revealed that of 28 cases that met criteria for sepsis, none was identified as such.

Since the hospital entered the project, an additional 61 patients screened positive. Of those, 59 had the severe sepsis tracker completed, 56 had blood cultures drawn prior to administration of broad-spectrum antibiotics, and 57 received broad-spectrum antibiotics within 1 hour of presentation.

Additionally, 22 of the 59 patients for whom the severe sepsis tracker was completed had hypotension, and 18 of those received a 20-mL/kg fluid bolus within 2 hours of diagnosis.

Overall, 54 of the 59 patients who had the severe sepsis tracker completed survived their hospitalization. Only 2 of 35 patients with severe sepsis (5.7%) required transfer to a larger facility because of deterioration in their condition, compared with 7 of 28 patients (25%) in the group from the 2009-2010 preproject chart review.

Numerous states across the United States, especially in the Midwest and Northwest, have rural populations of less than 86 per square mile, similar to Kansas, with 1.330 small facilities serving rural populations located many miles from the nearest referral hospital, and could benefit from this approach to sepsis resuscitation, Dr. Simpson said.

The need for attention to the problem of sepsis is apparent not only based on the high mortality rates, but also in the outcomes of focus group research showing that only 42% of responding physicians from rural settings consider themselves to be "very knowledgeable" about sepsis diagnosis, treatments, and complications; while the same percentage consider themselves "not too knowledgeable," 4% say they are not at all knowledgeable, and 12% say they aren’t sure how knowledgeable they are, he said.

Similarly, only 2% of respondents said they are extremely knowledgeable about the differences among uncomplicated sepsis, severe sepsis, and septic shock; 27% said they are very knowledgeable; 61% said they are not too knowledgeable; 4% said they are not at all knowledgeable; and 6% said they are unsure how knowledgeable they are.

Few respondents were familiar with the Early Goal-Directed Therapy protocol or the Surviving Sepsis Campaign, and most admitted that the likelihood of missed sepsis diagnoses is high at their institution.

Most (about 85%) agreed that additional training would be extremely beneficial.

Although several challenges and hurdles exist with respect to improving sepsis outcomes in rural settings, including staffing issues, the lack of recognition of the extent of the problem, and the fact that sepsis is not yet a Joint Commission core measure, the results thus far of the Kansas Sepsis Project suggest positive change is within reach, Dr. Simpson said.

For more information about the project, click here.

The Kansas Sepsis Project is supported by the One Breath Foundation in the form of the Third Eli Lilly Distinguished Scholar in Critical Care Medicine Award. Dr. Simpson reported having no relevant financial disclosures.

ATLANTA – Indacaterol significantly improves bronchodilation and health status in patients with chronic obstructive pulmonary disease, and is safe and well tolerated, according to findings from studies presented at the annual meeting of the American College of Chest Physicians.

In a pooled analysis of efficacy and safety data from two randomized controlled studies, the inhaled long-acting beta₂-agonist bronchodilator given at the approved dose of 75 mcg daily was found to be of benefit regardless of age, sex, smoking status, or severity of airflow limitation. In another analysis of pooled data, treatment was shown to have an acceptable cardiovascular and cerebrovascular safety profile.

The efficacy analysis included 640 patients from two identically designed studies who were randomized to receive indacaterol or placebo for 12 weeks. Trough (24 hours post dose) forced expiratory volume in 1 second (FEV₁) improved by least-squares mean differences of 150 and 110 mL among men and women, respectively; by 110 and 150 mL among those under age 65 and those aged 65 or older; by 150 and 110 mL among those with moderate and severe airflow limitation; and by 140 and 130 mL in ex-smokers and current smokers, Dr. Thomas Siler of Midwest Chest Consultants in St. Charles, Mo., reported.

Health status scores, as measured using the St. George’s Respiratory Questionnaire, improved similarly in men and women (by 3.8 and 3.7 units, respectively), and also improved in all of the other groups. Improvement was greater, however, in those aged 65 years and older (by 4.5 units vs. 3.3 units in those under age 65), those with severe airflow limitation (by 4.6 units vs. 3.3 units in those with moderate airflow limitation), and in ex-smokers (by 4.1 vs. 3.5 units in current smokers).

Adverse events occurred in 44%-57% of patients receiving indacaterol and in 40%-48% of patients receiving placebo. More adverse events in both groups occurred in older patients, women, those with moderate disease, and ex-smokers.

Patients in this study had a mean age of 63 years, and a mean post-albuterol FEV₁ of 54% predicted. About 40% were receiving inhaled corticosteroids.

The findings suggest that indacaterol can be successfully used to treat a range of COPD patients, Dr. Siler concluded. Treatment can be expected to lead to "substantial and worthwhile improvements in bronchodilation and health status," he added.

According to findings from a separate analysis of pooled data from nearly 2,500 patients, these improvements come without an increase in the risk of cerebro- and cardiovascular adverse events (CCV AEs).

The overall frequency of CCV AEs was similar in 449 patients treated for up to 3 months and 2,012 control patients who received placebo (2.0% and 2.58%, respectively), and no type of CCV AE occurred in more than 2 patients in the active treatment group, Dr. James Donohue reported.

Serious CCV AEs occurred in 2 patients in the treatment group and 13 in the placebo group, and an Antiplatelet Trialists’ Collaboration (APTC) event (a cerebrovascular accident not believed to be related to study treatment) occurred in 1 patient in the treatment group, compared with 8 patients in the control group, said Dr. Donohue of the University of North Carolina, Chapel Hill.

The overall frequency of patients with CCV AEs in a 6-month study population ranged from 3.3% to 5.8%, and no dose-response relationship was seen between the 75-mcg dose and up to 600 mcg daily for CCV AEs.

No deaths were reported in those receiving indacaterol 75.

These findings, which used pooled data from previous studies and a database of U.S. and Canadian patients, indicate that indacaterol given at the 75-mcg dose has an acceptable CCV safety profile in patients with moderate to severe COPD, Dr. Donohue said.

When considered in the context of the efficacy data, the findings should be very reassuring to clinicians, he concluded.

The studies included in the safety analysis were sponsored by Novartis. Dr. Donohue and Dr. Siler reported financial relationships with Novartis, which makes indacaterol, as well as with other industry companies. Dr. Donohue reported receiving fees for consulting and/or serving on speakers bureaus or advisory committees for Novartis, GSK, Boehringer-Ingelheim, and other companies. Dr. Siler reported receiving grant monies from GSK, Novartis, Boehringer-Ingelheim, and other companies. He also reported receiving fees for consulting, serving on speakers bureaus, and/or serving on advisory committees for Boehringer-Ingelheim, AstraZeneca, and Forest Research Institute.

ATLANTA – Indacaterol significantly improves bronchodilation and health status in patients with chronic obstructive pulmonary disease, and is safe and well tolerated, according to findings from studies presented at the annual meeting of the American College of Chest Physicians.

In a pooled analysis of efficacy and safety data from two randomized controlled studies, the inhaled long-acting beta₂-agonist bronchodilator given at the approved dose of 75 mcg daily was found to be of benefit regardless of age, sex, smoking status, or severity of airflow limitation. In another analysis of pooled data, treatment was shown to have an acceptable cardiovascular and cerebrovascular safety profile.

The efficacy analysis included 640 patients from two identically designed studies who were randomized to receive indacaterol or placebo for 12 weeks. Trough (24 hours post dose) forced expiratory volume in 1 second (FEV₁) improved by least-squares mean differences of 150 and 110 mL among men and women, respectively; by 110 and 150 mL among those under age 65 and those aged 65 or older; by 150 and 110 mL among those with moderate and severe airflow limitation; and by 140 and 130 mL in ex-smokers and current smokers, Dr. Thomas Siler of Midwest Chest Consultants in St. Charles, Mo., reported.

Health status scores, as measured using the St. George’s Respiratory Questionnaire, improved similarly in men and women (by 3.8 and 3.7 units, respectively), and also improved in all of the other groups. Improvement was greater, however, in those aged 65 years and older (by 4.5 units vs. 3.3 units in those under age 65), those with severe airflow limitation (by 4.6 units vs. 3.3 units in those with moderate airflow limitation), and in ex-smokers (by 4.1 vs. 3.5 units in current smokers).

Adverse events occurred in 44%-57% of patients receiving indacaterol and in 40%-48% of patients receiving placebo. More adverse events in both groups occurred in older patients, women, those with moderate disease, and ex-smokers.

Patients in this study had a mean age of 63 years, and a mean post-albuterol FEV₁ of 54% predicted. About 40% were receiving inhaled corticosteroids.

The findings suggest that indacaterol can be successfully used to treat a range of COPD patients, Dr. Siler concluded. Treatment can be expected to lead to "substantial and worthwhile improvements in bronchodilation and health status," he added.

According to findings from a separate analysis of pooled data from nearly 2,500 patients, these improvements come without an increase in the risk of cerebro- and cardiovascular adverse events (CCV AEs).

The overall frequency of CCV AEs was similar in 449 patients treated for up to 3 months and 2,012 control patients who received placebo (2.0% and 2.58%, respectively), and no type of CCV AE occurred in more than 2 patients in the active treatment group, Dr. James Donohue reported.

Serious CCV AEs occurred in 2 patients in the treatment group and 13 in the placebo group, and an Antiplatelet Trialists’ Collaboration (APTC) event (a cerebrovascular accident not believed to be related to study treatment) occurred in 1 patient in the treatment group, compared with 8 patients in the control group, said Dr. Donohue of the University of North Carolina, Chapel Hill.

The overall frequency of patients with CCV AEs in a 6-month study population ranged from 3.3% to 5.8%, and no dose-response relationship was seen between the 75-mcg dose and up to 600 mcg daily for CCV AEs.

No deaths were reported in those receiving indacaterol 75.

These findings, which used pooled data from previous studies and a database of U.S. and Canadian patients, indicate that indacaterol given at the 75-mcg dose has an acceptable CCV safety profile in patients with moderate to severe COPD, Dr. Donohue said.

When considered in the context of the efficacy data, the findings should be very reassuring to clinicians, he concluded.

The studies included in the safety analysis were sponsored by Novartis. Dr. Donohue and Dr. Siler reported financial relationships with Novartis, which makes indacaterol, as well as with other industry companies. Dr. Donohue reported receiving fees for consulting and/or serving on speakers bureaus or advisory committees for Novartis, GSK, Boehringer-Ingelheim, and other companies. Dr. Siler reported receiving grant monies from GSK, Novartis, Boehringer-Ingelheim, and other companies. He also reported receiving fees for consulting, serving on speakers bureaus, and/or serving on advisory committees for Boehringer-Ingelheim, AstraZeneca, and Forest Research Institute.

ATLANTA – Indacaterol significantly improves bronchodilation and health status in patients with chronic obstructive pulmonary disease, and is safe and well tolerated, according to findings from studies presented at the annual meeting of the American College of Chest Physicians.

In a pooled analysis of efficacy and safety data from two randomized controlled studies, the inhaled long-acting beta₂-agonist bronchodilator given at the approved dose of 75 mcg daily was found to be of benefit regardless of age, sex, smoking status, or severity of airflow limitation. In another analysis of pooled data, treatment was shown to have an acceptable cardiovascular and cerebrovascular safety profile.

The efficacy analysis included 640 patients from two identically designed studies who were randomized to receive indacaterol or placebo for 12 weeks. Trough (24 hours post dose) forced expiratory volume in 1 second (FEV₁) improved by least-squares mean differences of 150 and 110 mL among men and women, respectively; by 110 and 150 mL among those under age 65 and those aged 65 or older; by 150 and 110 mL among those with moderate and severe airflow limitation; and by 140 and 130 mL in ex-smokers and current smokers, Dr. Thomas Siler of Midwest Chest Consultants in St. Charles, Mo., reported.

Health status scores, as measured using the St. George’s Respiratory Questionnaire, improved similarly in men and women (by 3.8 and 3.7 units, respectively), and also improved in all of the other groups. Improvement was greater, however, in those aged 65 years and older (by 4.5 units vs. 3.3 units in those under age 65), those with severe airflow limitation (by 4.6 units vs. 3.3 units in those with moderate airflow limitation), and in ex-smokers (by 4.1 vs. 3.5 units in current smokers).

Adverse events occurred in 44%-57% of patients receiving indacaterol and in 40%-48% of patients receiving placebo. More adverse events in both groups occurred in older patients, women, those with moderate disease, and ex-smokers.

Patients in this study had a mean age of 63 years, and a mean post-albuterol FEV₁ of 54% predicted. About 40% were receiving inhaled corticosteroids.

The findings suggest that indacaterol can be successfully used to treat a range of COPD patients, Dr. Siler concluded. Treatment can be expected to lead to "substantial and worthwhile improvements in bronchodilation and health status," he added.

According to findings from a separate analysis of pooled data from nearly 2,500 patients, these improvements come without an increase in the risk of cerebro- and cardiovascular adverse events (CCV AEs).

The overall frequency of CCV AEs was similar in 449 patients treated for up to 3 months and 2,012 control patients who received placebo (2.0% and 2.58%, respectively), and no type of CCV AE occurred in more than 2 patients in the active treatment group, Dr. James Donohue reported.

Serious CCV AEs occurred in 2 patients in the treatment group and 13 in the placebo group, and an Antiplatelet Trialists’ Collaboration (APTC) event (a cerebrovascular accident not believed to be related to study treatment) occurred in 1 patient in the treatment group, compared with 8 patients in the control group, said Dr. Donohue of the University of North Carolina, Chapel Hill.

The overall frequency of patients with CCV AEs in a 6-month study population ranged from 3.3% to 5.8%, and no dose-response relationship was seen between the 75-mcg dose and up to 600 mcg daily for CCV AEs.

No deaths were reported in those receiving indacaterol 75.

These findings, which used pooled data from previous studies and a database of U.S. and Canadian patients, indicate that indacaterol given at the 75-mcg dose has an acceptable CCV safety profile in patients with moderate to severe COPD, Dr. Donohue said.

When considered in the context of the efficacy data, the findings should be very reassuring to clinicians, he concluded.

The studies included in the safety analysis were sponsored by Novartis. Dr. Donohue and Dr. Siler reported financial relationships with Novartis, which makes indacaterol, as well as with other industry companies. Dr. Donohue reported receiving fees for consulting and/or serving on speakers bureaus or advisory committees for Novartis, GSK, Boehringer-Ingelheim, and other companies. Dr. Siler reported receiving grant monies from GSK, Novartis, Boehringer-Ingelheim, and other companies. He also reported receiving fees for consulting, serving on speakers bureaus, and/or serving on advisory committees for Boehringer-Ingelheim, AstraZeneca, and Forest Research Institute.

ATLANTA – Regardless of disease severity, guideline-concordant treatment is not provided to nearly half of all patients who have stable chronic obstructive pulmonary disease and are treated in the ambulatory care setting, findings from an observational study suggest.

The study also indicated that guideline-concordant treatment was more likely to be provided when patients were comanaged by a pulmonologist and a primary care physician.

Of 450 patients, 56% received guideline-concordant care as outlined by the 2010 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage-specific recommendations, Dr. Gulshan Sharma reported at the annual meeting of the American College of Chest Physicians.

No differences were found in treatment level with respect to age, gender, race, disease severity, or comorbidities on multivariate analysis, but patients comanaged by a primary care physician and a pulmonologist were more likely to receive an appropriate level of care, as compared to patients treated by a primary care physician (odds ratio, 4.6), said Dr. Sharma of the University of Texas Medical Branch, Galveston.

Clinical practice guidelines for the treatment of patients with COPD in the ambulatory care setting are issued and updated regularly. Previous studies have demonstrated the value of these guidelines for improving the quality of care of patients with COPD and for reducing exacerbations and hospitalizations.

However, the degree to which these guidelines are implemented in clinical practice has been unclear, Dr. Sharma said. The study findings suggest that they are underutilized, particularly by primary care physicians.

Patients included in the study were adults with a clinical diagnosis of COPD and at least one outpatient visit between January and December 2010. The mean age of participants was 67 years, 46% were women, 20% had no comorbidities, and 75% had one or two comorbidities.

About 7% had GOLD stage I disease, almost half (more than 46%) had GOLD stage II disease, 33% had stage III disease, and 13% had stage IV disease.

Additionally, 47% were managed by a primary care physician alone, 41% were comanaged by a primary care physician and a pulmonologist, 10% did not have a primary care physician and received care mainly from a specialist, and about 2% had no regular care provider.

The findings indicate a need for efforts to increase awareness of clinical practice guidelines and the importance of adherence to the guidelines in patients with COPD, particularly among primary care physicians, Dr. Sharma concluded.

Dr. Sharma reported having no disclosures.

ATLANTA – Regardless of disease severity, guideline-concordant treatment is not provided to nearly half of all patients who have stable chronic obstructive pulmonary disease and are treated in the ambulatory care setting, findings from an observational study suggest.

The study also indicated that guideline-concordant treatment was more likely to be provided when patients were comanaged by a pulmonologist and a primary care physician.

Of 450 patients, 56% received guideline-concordant care as outlined by the 2010 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage-specific recommendations, Dr. Gulshan Sharma reported at the annual meeting of the American College of Chest Physicians.

No differences were found in treatment level with respect to age, gender, race, disease severity, or comorbidities on multivariate analysis, but patients comanaged by a primary care physician and a pulmonologist were more likely to receive an appropriate level of care, as compared to patients treated by a primary care physician (odds ratio, 4.6), said Dr. Sharma of the University of Texas Medical Branch, Galveston.

Clinical practice guidelines for the treatment of patients with COPD in the ambulatory care setting are issued and updated regularly. Previous studies have demonstrated the value of these guidelines for improving the quality of care of patients with COPD and for reducing exacerbations and hospitalizations.

However, the degree to which these guidelines are implemented in clinical practice has been unclear, Dr. Sharma said. The study findings suggest that they are underutilized, particularly by primary care physicians.

Patients included in the study were adults with a clinical diagnosis of COPD and at least one outpatient visit between January and December 2010. The mean age of participants was 67 years, 46% were women, 20% had no comorbidities, and 75% had one or two comorbidities.

About 7% had GOLD stage I disease, almost half (more than 46%) had GOLD stage II disease, 33% had stage III disease, and 13% had stage IV disease.

Additionally, 47% were managed by a primary care physician alone, 41% were comanaged by a primary care physician and a pulmonologist, 10% did not have a primary care physician and received care mainly from a specialist, and about 2% had no regular care provider.

The findings indicate a need for efforts to increase awareness of clinical practice guidelines and the importance of adherence to the guidelines in patients with COPD, particularly among primary care physicians, Dr. Sharma concluded.

Dr. Sharma reported having no disclosures.

ATLANTA – Regardless of disease severity, guideline-concordant treatment is not provided to nearly half of all patients who have stable chronic obstructive pulmonary disease and are treated in the ambulatory care setting, findings from an observational study suggest.

The study also indicated that guideline-concordant treatment was more likely to be provided when patients were comanaged by a pulmonologist and a primary care physician.

Of 450 patients, 56% received guideline-concordant care as outlined by the 2010 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage-specific recommendations, Dr. Gulshan Sharma reported at the annual meeting of the American College of Chest Physicians.

No differences were found in treatment level with respect to age, gender, race, disease severity, or comorbidities on multivariate analysis, but patients comanaged by a primary care physician and a pulmonologist were more likely to receive an appropriate level of care, as compared to patients treated by a primary care physician (odds ratio, 4.6), said Dr. Sharma of the University of Texas Medical Branch, Galveston.

Clinical practice guidelines for the treatment of patients with COPD in the ambulatory care setting are issued and updated regularly. Previous studies have demonstrated the value of these guidelines for improving the quality of care of patients with COPD and for reducing exacerbations and hospitalizations.

However, the degree to which these guidelines are implemented in clinical practice has been unclear, Dr. Sharma said. The study findings suggest that they are underutilized, particularly by primary care physicians.

Patients included in the study were adults with a clinical diagnosis of COPD and at least one outpatient visit between January and December 2010. The mean age of participants was 67 years, 46% were women, 20% had no comorbidities, and 75% had one or two comorbidities.

About 7% had GOLD stage I disease, almost half (more than 46%) had GOLD stage II disease, 33% had stage III disease, and 13% had stage IV disease.

Additionally, 47% were managed by a primary care physician alone, 41% were comanaged by a primary care physician and a pulmonologist, 10% did not have a primary care physician and received care mainly from a specialist, and about 2% had no regular care provider.

The findings indicate a need for efforts to increase awareness of clinical practice guidelines and the importance of adherence to the guidelines in patients with COPD, particularly among primary care physicians, Dr. Sharma concluded.

Dr. Sharma reported having no disclosures.

ATLANTA – Data suggest that only about a third of patients hospitalized for chronic obstructive pulmonary disease receive appropriate care, but a number of steps – beginning with decisions about when to admit and ending with proper discharge management – can be taken to improve outcomes, according to Dr. Darcy Marciniuk.

Although scientific guidance on when patients should be admitted is lacking, guidelines and consensus statements suggest that patients with an exacerbation should be admitted:

• If they experience a marked increase in dyspnea.

• If they have severe underlying COPD with little reserve, "such that there’s no room for error."

• If they fail to respond to initial management.

• If they have comorbidities, including heart failure, arrhythmias, or renal impairment.

• If they have advanced age.

• If they experience frequent severe exacerbations.

• If they have insufficient home support.

Once a patient is admitted, controlled appropriate supplemental oxygen should be administered as directed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, noninvasive ventilation should be used when indicated, aggressive therapies should be used at the outset, and use of antibiotics or systemic corticosteroids should be considered, said Dr. Marciniuk, AACP president, and head of the division of respirology, critical care, and sleep medicine at the University of Saskatchewan, Saskatoon, Canada.

An effort should also be made to identify the precipitating factor, to recognize and optimize, or prevent comorbid conditions, to prevent complications, and to address depressions and anxiety, he said.

With respect to supplemental oxygen, the GOLD guidelines will help ensure there is "always enough, but never too much," Dr. Marciniuk said.

"Now, with saturation monitors, life is good; it’s very easy to make sure patients receive appropriate therapy," he added.

He also spotlighted noninvasive ventilation. It has revolutionized in-hospital COPD management, lowering intubation rates by 60% and substantially decreasing in-hospital mortality, he said.

"Noninvasive ventilation has been incredible for our patients," he said.

Although it was first used in the 1980s, it is now "really the treatment of choice for acute hypercapnic respiratory failure in this setting," he added.

Contrary to some beliefs about outcomes with COPD in the intensive care unit, mortality is actually much lower than for many other conditions. For example, mortality in COPD patients in the ICU is about half that of patients with sepsis or acute respiratory distress syndrome.

"So, even though a patient may look short of breath, and someone may think they have a poor quality of life, it is the patients who should be judging that," he said, adding: "There needs to be that comfort, that back-up, of the ICU, because data would suggest the outcomes are pretty good."

There is significant evidence of benefit with the use of noninvasive ventilation, particularly with respiratory acidosis of pH less than 7.35, PCO₂ greater than 45, and significant dyspnea, which is easily detected by clinical means, he added.

Depression in COPD patients is also particularly important to address.

Studies show that patients with depression have longer hospital stays (twice as long, according to one observational study), more frequent exacerbations in the year following discharge, and higher mortality rates, he said, acknowledging that "our understanding of the co-presence of depression and anxiety (in COPD patients) is growing, but our understanding that it appears to [have an impact] in this setting is also growing."

As for discharge planning, appropriate methods and practices must be put in place for reducing the future risk of acute exacerbations, he said.

Dr. Marciniuk reported having no financial disclosures, with the exception of research funding directed to and managed by his institution.

ATLANTA – Data suggest that only about a third of patients hospitalized for chronic obstructive pulmonary disease receive appropriate care, but a number of steps – beginning with decisions about when to admit and ending with proper discharge management – can be taken to improve outcomes, according to Dr. Darcy Marciniuk.

Although scientific guidance on when patients should be admitted is lacking, guidelines and consensus statements suggest that patients with an exacerbation should be admitted:

• If they experience a marked increase in dyspnea.

• If they have severe underlying COPD with little reserve, "such that there’s no room for error."

• If they fail to respond to initial management.

• If they have comorbidities, including heart failure, arrhythmias, or renal impairment.

• If they have advanced age.

• If they experience frequent severe exacerbations.

• If they have insufficient home support.

Once a patient is admitted, controlled appropriate supplemental oxygen should be administered as directed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, noninvasive ventilation should be used when indicated, aggressive therapies should be used at the outset, and use of antibiotics or systemic corticosteroids should be considered, said Dr. Marciniuk, AACP president, and head of the division of respirology, critical care, and sleep medicine at the University of Saskatchewan, Saskatoon, Canada.

An effort should also be made to identify the precipitating factor, to recognize and optimize, or prevent comorbid conditions, to prevent complications, and to address depressions and anxiety, he said.

With respect to supplemental oxygen, the GOLD guidelines will help ensure there is "always enough, but never too much," Dr. Marciniuk said.

"Now, with saturation monitors, life is good; it’s very easy to make sure patients receive appropriate therapy," he added.

He also spotlighted noninvasive ventilation. It has revolutionized in-hospital COPD management, lowering intubation rates by 60% and substantially decreasing in-hospital mortality, he said.

"Noninvasive ventilation has been incredible for our patients," he said.

Although it was first used in the 1980s, it is now "really the treatment of choice for acute hypercapnic respiratory failure in this setting," he added.

Contrary to some beliefs about outcomes with COPD in the intensive care unit, mortality is actually much lower than for many other conditions. For example, mortality in COPD patients in the ICU is about half that of patients with sepsis or acute respiratory distress syndrome.

"So, even though a patient may look short of breath, and someone may think they have a poor quality of life, it is the patients who should be judging that," he said, adding: "There needs to be that comfort, that back-up, of the ICU, because data would suggest the outcomes are pretty good."

There is significant evidence of benefit with the use of noninvasive ventilation, particularly with respiratory acidosis of pH less than 7.35, PCO₂ greater than 45, and significant dyspnea, which is easily detected by clinical means, he added.

Depression in COPD patients is also particularly important to address.

Studies show that patients with depression have longer hospital stays (twice as long, according to one observational study), more frequent exacerbations in the year following discharge, and higher mortality rates, he said, acknowledging that "our understanding of the co-presence of depression and anxiety (in COPD patients) is growing, but our understanding that it appears to [have an impact] in this setting is also growing."

As for discharge planning, appropriate methods and practices must be put in place for reducing the future risk of acute exacerbations, he said.

Dr. Marciniuk reported having no financial disclosures, with the exception of research funding directed to and managed by his institution.

ATLANTA – Data suggest that only about a third of patients hospitalized for chronic obstructive pulmonary disease receive appropriate care, but a number of steps – beginning with decisions about when to admit and ending with proper discharge management – can be taken to improve outcomes, according to Dr. Darcy Marciniuk.

Although scientific guidance on when patients should be admitted is lacking, guidelines and consensus statements suggest that patients with an exacerbation should be admitted:

• If they experience a marked increase in dyspnea.

• If they have severe underlying COPD with little reserve, "such that there’s no room for error."

• If they fail to respond to initial management.

• If they have comorbidities, including heart failure, arrhythmias, or renal impairment.

• If they have advanced age.

• If they experience frequent severe exacerbations.

• If they have insufficient home support.

Once a patient is admitted, controlled appropriate supplemental oxygen should be administered as directed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, noninvasive ventilation should be used when indicated, aggressive therapies should be used at the outset, and use of antibiotics or systemic corticosteroids should be considered, said Dr. Marciniuk, AACP president, and head of the division of respirology, critical care, and sleep medicine at the University of Saskatchewan, Saskatoon, Canada.

An effort should also be made to identify the precipitating factor, to recognize and optimize, or prevent comorbid conditions, to prevent complications, and to address depressions and anxiety, he said.

With respect to supplemental oxygen, the GOLD guidelines will help ensure there is "always enough, but never too much," Dr. Marciniuk said.

"Now, with saturation monitors, life is good; it’s very easy to make sure patients receive appropriate therapy," he added.

He also spotlighted noninvasive ventilation. It has revolutionized in-hospital COPD management, lowering intubation rates by 60% and substantially decreasing in-hospital mortality, he said.

"Noninvasive ventilation has been incredible for our patients," he said.

Although it was first used in the 1980s, it is now "really the treatment of choice for acute hypercapnic respiratory failure in this setting," he added.

Contrary to some beliefs about outcomes with COPD in the intensive care unit, mortality is actually much lower than for many other conditions. For example, mortality in COPD patients in the ICU is about half that of patients with sepsis or acute respiratory distress syndrome.

"So, even though a patient may look short of breath, and someone may think they have a poor quality of life, it is the patients who should be judging that," he said, adding: "There needs to be that comfort, that back-up, of the ICU, because data would suggest the outcomes are pretty good."

There is significant evidence of benefit with the use of noninvasive ventilation, particularly with respiratory acidosis of pH less than 7.35, PCO₂ greater than 45, and significant dyspnea, which is easily detected by clinical means, he added.

Depression in COPD patients is also particularly important to address.

Studies show that patients with depression have longer hospital stays (twice as long, according to one observational study), more frequent exacerbations in the year following discharge, and higher mortality rates, he said, acknowledging that "our understanding of the co-presence of depression and anxiety (in COPD patients) is growing, but our understanding that it appears to [have an impact] in this setting is also growing."

As for discharge planning, appropriate methods and practices must be put in place for reducing the future risk of acute exacerbations, he said.

Dr. Marciniuk reported having no financial disclosures, with the exception of research funding directed to and managed by his institution.

ATLANTA – Medical thoracoscopy is safe and feasible for performing lung biopsy in patients with diffuse parenchymal lung disease of unknown etiology on high-resolution computed tomography. And the approach could serve as an alternative to surgical biopsy in some patients, findings from a prospective study suggest.

In 10 patients who underwent medical thoracoscopic lung biopsies as part of the study, good biopsy specimens, with an average size of 0.5 x 0.4 cm were obtained, Dr. Mohamed Elnady said at the annual meeting of the American College of Chest Physicians.

Complications with this advanced technique included persistent air leak for 5-7 days in two patients, pneumothorax after removal of the intercostals tube in two patients, pain in six patients, and minor bleeding in one patient. The air leaks resolved spontaneously, and the pneumothoraces resolved with administration of high flow oxygen, said Dr. Elnady of Cairo (Egypt) University Hospitals.

The mean duration of intercostal tube placement was 3.1 days, with a range of 1-7 days; no infection, respiratory failure requiring intensive care unit admission, or mortality occurred within 30 days after the procedure, he noted.

Patients in the study included four women and six men with a mean age of 42 years. The lung biopsies obtained via medical thoracoscopy were sent for histopathologic examination, and patients underwent follow-up by chest x-ray for confirmation of lung expansion, as well as observation of the intercostal tube to detect complications. Among the ultimate diagnoses were metastatic adenocarcinoma, interstitial lung disease, and lymphangioleiomyomatosis.

"Thoracosopic lung biopsy by medical thoracoscopy is useful in the diagnosis of patient with diffuse pulmonary infiltrates of unknown etiology when lung biopsy is needed for an accurate diagnosis," Dr. Elnady concluded, noting that while the procedure does carry a risk of certain non–life-threatening complications, these can be minimized with good patient selection.

Commenting on the findings, Dr. Muthiah P. Muthiah, who moderated the session, said this novel approach to obtaining a lung biopsy is of interest, but also "something we still have to get comfortable with."

"I’m not ready to do this yet, but this is something to consider ... you will want to certainly do this with a surgeon’s back-up in your institution," said Dr. Muthiah of the University of Tennessee Health Science Center, Memphis.

Neither Dr. Muthiah nor Dr. Elnady had disclosures to report.

ATLANTA – Medical thoracoscopy is safe and feasible for performing lung biopsy in patients with diffuse parenchymal lung disease of unknown etiology on high-resolution computed tomography. And the approach could serve as an alternative to surgical biopsy in some patients, findings from a prospective study suggest.

In 10 patients who underwent medical thoracoscopic lung biopsies as part of the study, good biopsy specimens, with an average size of 0.5 x 0.4 cm were obtained, Dr. Mohamed Elnady said at the annual meeting of the American College of Chest Physicians.

Complications with this advanced technique included persistent air leak for 5-7 days in two patients, pneumothorax after removal of the intercostals tube in two patients, pain in six patients, and minor bleeding in one patient. The air leaks resolved spontaneously, and the pneumothoraces resolved with administration of high flow oxygen, said Dr. Elnady of Cairo (Egypt) University Hospitals.

The mean duration of intercostal tube placement was 3.1 days, with a range of 1-7 days; no infection, respiratory failure requiring intensive care unit admission, or mortality occurred within 30 days after the procedure, he noted.

Patients in the study included four women and six men with a mean age of 42 years. The lung biopsies obtained via medical thoracoscopy were sent for histopathologic examination, and patients underwent follow-up by chest x-ray for confirmation of lung expansion, as well as observation of the intercostal tube to detect complications. Among the ultimate diagnoses were metastatic adenocarcinoma, interstitial lung disease, and lymphangioleiomyomatosis.

"Thoracosopic lung biopsy by medical thoracoscopy is useful in the diagnosis of patient with diffuse pulmonary infiltrates of unknown etiology when lung biopsy is needed for an accurate diagnosis," Dr. Elnady concluded, noting that while the procedure does carry a risk of certain non–life-threatening complications, these can be minimized with good patient selection.

Commenting on the findings, Dr. Muthiah P. Muthiah, who moderated the session, said this novel approach to obtaining a lung biopsy is of interest, but also "something we still have to get comfortable with."

"I’m not ready to do this yet, but this is something to consider ... you will want to certainly do this with a surgeon’s back-up in your institution," said Dr. Muthiah of the University of Tennessee Health Science Center, Memphis.

Neither Dr. Muthiah nor Dr. Elnady had disclosures to report.

ATLANTA – Medical thoracoscopy is safe and feasible for performing lung biopsy in patients with diffuse parenchymal lung disease of unknown etiology on high-resolution computed tomography. And the approach could serve as an alternative to surgical biopsy in some patients, findings from a prospective study suggest.

In 10 patients who underwent medical thoracoscopic lung biopsies as part of the study, good biopsy specimens, with an average size of 0.5 x 0.4 cm were obtained, Dr. Mohamed Elnady said at the annual meeting of the American College of Chest Physicians.

Complications with this advanced technique included persistent air leak for 5-7 days in two patients, pneumothorax after removal of the intercostals tube in two patients, pain in six patients, and minor bleeding in one patient. The air leaks resolved spontaneously, and the pneumothoraces resolved with administration of high flow oxygen, said Dr. Elnady of Cairo (Egypt) University Hospitals.

The mean duration of intercostal tube placement was 3.1 days, with a range of 1-7 days; no infection, respiratory failure requiring intensive care unit admission, or mortality occurred within 30 days after the procedure, he noted.

Patients in the study included four women and six men with a mean age of 42 years. The lung biopsies obtained via medical thoracoscopy were sent for histopathologic examination, and patients underwent follow-up by chest x-ray for confirmation of lung expansion, as well as observation of the intercostal tube to detect complications. Among the ultimate diagnoses were metastatic adenocarcinoma, interstitial lung disease, and lymphangioleiomyomatosis.

"Thoracosopic lung biopsy by medical thoracoscopy is useful in the diagnosis of patient with diffuse pulmonary infiltrates of unknown etiology when lung biopsy is needed for an accurate diagnosis," Dr. Elnady concluded, noting that while the procedure does carry a risk of certain non–life-threatening complications, these can be minimized with good patient selection.

Commenting on the findings, Dr. Muthiah P. Muthiah, who moderated the session, said this novel approach to obtaining a lung biopsy is of interest, but also "something we still have to get comfortable with."

"I’m not ready to do this yet, but this is something to consider ... you will want to certainly do this with a surgeon’s back-up in your institution," said Dr. Muthiah of the University of Tennessee Health Science Center, Memphis.

Neither Dr. Muthiah nor Dr. Elnady had disclosures to report.

ATLANTA  – Long-term nocturnal use of noninvasive positive pressure ventilation significantly reduced the likelihood of intensive care unit admission in patients with severe stable chronic obstructive pulmonary disease, according to findings from a systematic review of 582 patients in 13 randomized, controlled clinical trials.

After 1 year, noninvasive positive pressure ventilation (NIPPV) was associated with a significant decrease in ICU admissions (odds ratio, 0.41) compared with standard medical therapy. Patients using NIPPV for more than 3 months also had improvements in oxygenation (mean difference of -2.43 mm Hg), reduction in PCO₂ (mean difference, -2.96 mm Hg), and an improvement in 6-minute walk distance (mean difference 45.15 m), Dr. Monali Patil reported at the annual meeting of the American College of Chest Physicians.

A trend toward improved mortality at 1 year did not reach statistical significance, and no significant improvements in lung function were noted, said Dr. Patil of the University at Buffalo (N.Y.).

Dr. Patil selected the 13 trials from a review of more than 700 studies conducted between 1991 and 2011. The analysis included only randomized, controlled trials of COPD patients who had an FEV₁ less than 50% of predicted and a PCO₂ greater than 45 mm Hg and were receiving bilevel positive airway pressure (BIPAP). The patients in the studies were aged 18-75 years, and had no COPD exacerbations within 2 weeks prior to study enrollment.

The long-term use of NIPPV in patients with severe stable COPD has been controversial, but these findings demonstrate significant benefits.

"So NIPPV can be used as adjuvant treatment for management of severe stable COPD patients," she concluded.

Dr Patil reported having no financial disclosures.

ATLANTA  – Long-term nocturnal use of noninvasive positive pressure ventilation significantly reduced the likelihood of intensive care unit admission in patients with severe stable chronic obstructive pulmonary disease, according to findings from a systematic review of 582 patients in 13 randomized, controlled clinical trials.

After 1 year, noninvasive positive pressure ventilation (NIPPV) was associated with a significant decrease in ICU admissions (odds ratio, 0.41) compared with standard medical therapy. Patients using NIPPV for more than 3 months also had improvements in oxygenation (mean difference of -2.43 mm Hg), reduction in PCO₂ (mean difference, -2.96 mm Hg), and an improvement in 6-minute walk distance (mean difference 45.15 m), Dr. Monali Patil reported at the annual meeting of the American College of Chest Physicians.

A trend toward improved mortality at 1 year did not reach statistical significance, and no significant improvements in lung function were noted, said Dr. Patil of the University at Buffalo (N.Y.).

Dr. Patil selected the 13 trials from a review of more than 700 studies conducted between 1991 and 2011. The analysis included only randomized, controlled trials of COPD patients who had an FEV₁ less than 50% of predicted and a PCO₂ greater than 45 mm Hg and were receiving bilevel positive airway pressure (BIPAP). The patients in the studies were aged 18-75 years, and had no COPD exacerbations within 2 weeks prior to study enrollment.

The long-term use of NIPPV in patients with severe stable COPD has been controversial, but these findings demonstrate significant benefits.

"So NIPPV can be used as adjuvant treatment for management of severe stable COPD patients," she concluded.

Dr Patil reported having no financial disclosures.

ATLANTA  – Long-term nocturnal use of noninvasive positive pressure ventilation significantly reduced the likelihood of intensive care unit admission in patients with severe stable chronic obstructive pulmonary disease, according to findings from a systematic review of 582 patients in 13 randomized, controlled clinical trials.

After 1 year, noninvasive positive pressure ventilation (NIPPV) was associated with a significant decrease in ICU admissions (odds ratio, 0.41) compared with standard medical therapy. Patients using NIPPV for more than 3 months also had improvements in oxygenation (mean difference of -2.43 mm Hg), reduction in PCO₂ (mean difference, -2.96 mm Hg), and an improvement in 6-minute walk distance (mean difference 45.15 m), Dr. Monali Patil reported at the annual meeting of the American College of Chest Physicians.

A trend toward improved mortality at 1 year did not reach statistical significance, and no significant improvements in lung function were noted, said Dr. Patil of the University at Buffalo (N.Y.).

Dr. Patil selected the 13 trials from a review of more than 700 studies conducted between 1991 and 2011. The analysis included only randomized, controlled trials of COPD patients who had an FEV₁ less than 50% of predicted and a PCO₂ greater than 45 mm Hg and were receiving bilevel positive airway pressure (BIPAP). The patients in the studies were aged 18-75 years, and had no COPD exacerbations within 2 weeks prior to study enrollment.

The long-term use of NIPPV in patients with severe stable COPD has been controversial, but these findings demonstrate significant benefits.

"So NIPPV can be used as adjuvant treatment for management of severe stable COPD patients," she concluded.

Dr Patil reported having no financial disclosures.

ATLANTA – Macitentan, a novel dual endothelin receptor antagonist with enhanced tissue penetration, significantly improves morbidity and mortality in patients with pulmonary arterial hypertension, according to findings from an industry-sponsored, randomized controlled phase III SERAPHIN study.

Macitentan treatment reduced the risk of occurrence of combined morbidity and mortality events by 30% in 250 patients randomized to receive 3 mg once daily and by 45% in 242 patients randomized to receive 10 mg once daily, compared with 250 patients who received placebo, Dr. Lewis Rubin reported at the annual meeting of the American College of Chest Physicians.

The differences were highly significant for both macitentan doses, and the effect of treatment on this novel primary end point was observed irrespective of background therapy, which consisted mainly of phosphodiesterase type-5 (PDE-5) inhibitors.

Among patients using background therapy, risk was reduced by 17% and 38% for the 3 mg and 10 mg groups, respectively; in treatment-naive patients, the risk was reduced by 47% and 55% in the dosage groups, respectively, said Dr. Rubin of the University of California, San Diego.

The findings hold promise for improved long-term outcomes in patients with pulmonary arterial hypertension (PAH), Dr. Rubin said. "This primary morbidity/mortality end point captures clinically relevant events that reflect true disease progression," he noted, explaining that the end point included time to death, atrial septostomy, lung transplantation, initiation of intravenous/subcutaneous prostanoids, or worsening of PAH.

To meet the criteria for PAH worsening, participants had to experience a confirmed 15% or greater decrease in 6-minute walk distance and worsening of symptoms as defined by either a worsening in functional class, worsening symptoms of right heart failure, need for a new PAH treatment, or need for an intravenous diuretic. The majority of events contributing to achievement of the primary end point were associated with worsening of PAH, rather than death, he noted.

In addition to improvements with respect to the primary end point, macitentan treatment also was associated with improvement on the secondary end point of the composite of mortality or hospitalization due to PAH, with risk reduction of 33% and 50% in the 3-mg and 10-mg groups, respectively, compared with placebo, Dr. Rubin said.

Macitentan was well tolerated, with both the treatment group and the placebo group experiencing similar incidences of elevated liver aminotransferases and peripheral edema, although headache, nasopharyngitis, and anemia all occurred more frequently in the treatment groups.

Participants in the double-blind, event-driven SERAPHIN study (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) were individuals aged 12 years or older with PAH. Randomization began in May of 2008, and study end was predefined as the occurrence of 285 morbidity/mortality events, which occurred as of March 2012.

The findings are notable because existing PAH therapies, including bosentan and ambrisentan, have been approved based only on short-term trials with exercise capacity as the primary end point, and have potential for adverse events that can limit tolerability, Dr. Rubin said.

"So an endothelin receptor antagonist that has a better tolerability profile would be potentially desirable," he said.

Indeed, macitentan, which is a product of a tailored discovery program, has not only been shown to have enhanced tissue penetration and "superior in vivo efficacy in a number of animal models," but also to have no effect on bile salts. It, therefore, has diminished adverse effects on the rate of hepatic dysfunction that is seen, with varying degrees, as a manifestation of endothelin receptor antagonism, he explained.

"In addition, it has demonstrated unique sustained receptor binding, which also may be beneficial in long-term therapy," he said.

The SERAPHIN study was sponsored by Actelion, the maker of macitentan. Dr. Rubin disclosed that he has received payment for consulting and/or serving on speaker bureaus or advisory committees for Actelion, Pfizer, United Therapeutics, Lung LLC, Gilead, GlaxoSmithKline, Bayer, and GeNo.

ATLANTA – Macitentan, a novel dual endothelin receptor antagonist with enhanced tissue penetration, significantly improves morbidity and mortality in patients with pulmonary arterial hypertension, according to findings from an industry-sponsored, randomized controlled phase III SERAPHIN study.

Macitentan treatment reduced the risk of occurrence of combined morbidity and mortality events by 30% in 250 patients randomized to receive 3 mg once daily and by 45% in 242 patients randomized to receive 10 mg once daily, compared with 250 patients who received placebo, Dr. Lewis Rubin reported at the annual meeting of the American College of Chest Physicians.

The differences were highly significant for both macitentan doses, and the effect of treatment on this novel primary end point was observed irrespective of background therapy, which consisted mainly of phosphodiesterase type-5 (PDE-5) inhibitors.

Among patients using background therapy, risk was reduced by 17% and 38% for the 3 mg and 10 mg groups, respectively; in treatment-naive patients, the risk was reduced by 47% and 55% in the dosage groups, respectively, said Dr. Rubin of the University of California, San Diego.

The findings hold promise for improved long-term outcomes in patients with pulmonary arterial hypertension (PAH), Dr. Rubin said. "This primary morbidity/mortality end point captures clinically relevant events that reflect true disease progression," he noted, explaining that the end point included time to death, atrial septostomy, lung transplantation, initiation of intravenous/subcutaneous prostanoids, or worsening of PAH.

To meet the criteria for PAH worsening, participants had to experience a confirmed 15% or greater decrease in 6-minute walk distance and worsening of symptoms as defined by either a worsening in functional class, worsening symptoms of right heart failure, need for a new PAH treatment, or need for an intravenous diuretic. The majority of events contributing to achievement of the primary end point were associated with worsening of PAH, rather than death, he noted.

In addition to improvements with respect to the primary end point, macitentan treatment also was associated with improvement on the secondary end point of the composite of mortality or hospitalization due to PAH, with risk reduction of 33% and 50% in the 3-mg and 10-mg groups, respectively, compared with placebo, Dr. Rubin said.

Macitentan was well tolerated, with both the treatment group and the placebo group experiencing similar incidences of elevated liver aminotransferases and peripheral edema, although headache, nasopharyngitis, and anemia all occurred more frequently in the treatment groups.

Participants in the double-blind, event-driven SERAPHIN study (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) were individuals aged 12 years or older with PAH. Randomization began in May of 2008, and study end was predefined as the occurrence of 285 morbidity/mortality events, which occurred as of March 2012.

The findings are notable because existing PAH therapies, including bosentan and ambrisentan, have been approved based only on short-term trials with exercise capacity as the primary end point, and have potential for adverse events that can limit tolerability, Dr. Rubin said.

"So an endothelin receptor antagonist that has a better tolerability profile would be potentially desirable," he said.

Indeed, macitentan, which is a product of a tailored discovery program, has not only been shown to have enhanced tissue penetration and "superior in vivo efficacy in a number of animal models," but also to have no effect on bile salts. It, therefore, has diminished adverse effects on the rate of hepatic dysfunction that is seen, with varying degrees, as a manifestation of endothelin receptor antagonism, he explained.

"In addition, it has demonstrated unique sustained receptor binding, which also may be beneficial in long-term therapy," he said.

The SERAPHIN study was sponsored by Actelion, the maker of macitentan. Dr. Rubin disclosed that he has received payment for consulting and/or serving on speaker bureaus or advisory committees for Actelion, Pfizer, United Therapeutics, Lung LLC, Gilead, GlaxoSmithKline, Bayer, and GeNo.

ATLANTA – Macitentan, a novel dual endothelin receptor antagonist with enhanced tissue penetration, significantly improves morbidity and mortality in patients with pulmonary arterial hypertension, according to findings from an industry-sponsored, randomized controlled phase III SERAPHIN study.

Macitentan treatment reduced the risk of occurrence of combined morbidity and mortality events by 30% in 250 patients randomized to receive 3 mg once daily and by 45% in 242 patients randomized to receive 10 mg once daily, compared with 250 patients who received placebo, Dr. Lewis Rubin reported at the annual meeting of the American College of Chest Physicians.

The differences were highly significant for both macitentan doses, and the effect of treatment on this novel primary end point was observed irrespective of background therapy, which consisted mainly of phosphodiesterase type-5 (PDE-5) inhibitors.

Among patients using background therapy, risk was reduced by 17% and 38% for the 3 mg and 10 mg groups, respectively; in treatment-naive patients, the risk was reduced by 47% and 55% in the dosage groups, respectively, said Dr. Rubin of the University of California, San Diego.

The findings hold promise for improved long-term outcomes in patients with pulmonary arterial hypertension (PAH), Dr. Rubin said. "This primary morbidity/mortality end point captures clinically relevant events that reflect true disease progression," he noted, explaining that the end point included time to death, atrial septostomy, lung transplantation, initiation of intravenous/subcutaneous prostanoids, or worsening of PAH.

To meet the criteria for PAH worsening, participants had to experience a confirmed 15% or greater decrease in 6-minute walk distance and worsening of symptoms as defined by either a worsening in functional class, worsening symptoms of right heart failure, need for a new PAH treatment, or need for an intravenous diuretic. The majority of events contributing to achievement of the primary end point were associated with worsening of PAH, rather than death, he noted.

In addition to improvements with respect to the primary end point, macitentan treatment also was associated with improvement on the secondary end point of the composite of mortality or hospitalization due to PAH, with risk reduction of 33% and 50% in the 3-mg and 10-mg groups, respectively, compared with placebo, Dr. Rubin said.

Macitentan was well tolerated, with both the treatment group and the placebo group experiencing similar incidences of elevated liver aminotransferases and peripheral edema, although headache, nasopharyngitis, and anemia all occurred more frequently in the treatment groups.

Participants in the double-blind, event-driven SERAPHIN study (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) were individuals aged 12 years or older with PAH. Randomization began in May of 2008, and study end was predefined as the occurrence of 285 morbidity/mortality events, which occurred as of March 2012.

The findings are notable because existing PAH therapies, including bosentan and ambrisentan, have been approved based only on short-term trials with exercise capacity as the primary end point, and have potential for adverse events that can limit tolerability, Dr. Rubin said.

"So an endothelin receptor antagonist that has a better tolerability profile would be potentially desirable," he said.

Indeed, macitentan, which is a product of a tailored discovery program, has not only been shown to have enhanced tissue penetration and "superior in vivo efficacy in a number of animal models," but also to have no effect on bile salts. It, therefore, has diminished adverse effects on the rate of hepatic dysfunction that is seen, with varying degrees, as a manifestation of endothelin receptor antagonism, he explained.

"In addition, it has demonstrated unique sustained receptor binding, which also may be beneficial in long-term therapy," he said.

The SERAPHIN study was sponsored by Actelion, the maker of macitentan. Dr. Rubin disclosed that he has received payment for consulting and/or serving on speaker bureaus or advisory committees for Actelion, Pfizer, United Therapeutics, Lung LLC, Gilead, GlaxoSmithKline, Bayer, and GeNo.

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.

ATLANTA – The combined use of a novel bronchial airway gene-expression test and bronchoscopy improves the ability to rule out lung cancer in patients with benign disease, compared with bronchoscopy alone, according to findings from the prospective case-controlled AEGIS-1 trial.

Because bronchoscopy, which plays a central role in lung cancer diagnosis, has varying diagnostic yield based on factors such as the size and location of the lesion, the method used to collect cells, and pathological processing methods, the findings suggest that the test (BronchoGen) could minimize the need for additional invasive procedures in these patients, Duncan Whitney, Ph.D., said at the annual meeting of the American College of Chest Physicians.

The AEGIS-1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer 1) trial included more than 700 current or former smokers undergoing bronchoscopy for suspicion of lung cancer. It was designed to evaluate the diagnostic accuracy of the genomic test, which detects gene expression of cytologically normal bronchial airway epithelial cells.

The investigators collected mainstem bronchial airway brushings from 330 patients, including 240 with confirmed primary lung cancer and 90 controls, and performed microarray analysis. The sample set was then split into an independent training sample of 220 cases and a test set of 110 cases, and the gene-expression prediction model was optimized.

Next, reverse transcription polymerase chain reaction (RT-PCR) assays were developed for candidate biomarker genes, and a multivariate test algorithm was reoptimized using the RT-PCR data generated by a reanalysis of 153 of the samples from cancer patients and 64 of the samples from controls, explained Dr. Whitney.

The test, which ultimately focused on 30 genes, yielded a sensitivity of 77%, compared with 74% for bronchoscopy alone. The combined use of the test and bronchoscopy yielded a sensitivity of 96% and a specificity of 73%.

The negative predictive value of the combined test also was better than that of bronchoscopy alone (0.85 vs. 0.65, respectively), said Dr. Whitney.

"So in essence, we’re reducing the false negative rate from 26% down to 4%," he said.

The BronchoGen test was developed based on the airway "field of injury" principle, which refers to the common molecular response that occurs throughout the respiratory tract in current and former smokers with lung cancer, Dr. Whitney explained.

These changes are detected in a gene-expression signature from normal airway cells, even decades after smoking cessation, he noted.

Despite tremendous work done in this area, which has dramatically improved the diagnostic yield and sensitivity of bronchoscopy in the past few years, the procedure is either inconclusive or not diagnostic in up to 50% of cases, he said.

Thus, a "fairly large need" exists in the medical community, given that about 300,000 bronchoscopy procedures are performed each year for suspicion of lung cancer, he added.

Complete results from AEGIS-1, as well as clinical validation of the BronchoGen test, are expected to be released later this year. An additional 1,300 patients have been enrolled in the ongoing AEGIS-II trial.

Allegro Diagnostics, which developed the BronchoGen test, reports that it plans to commercialize it for use with bronchoscopy beginning in 2013.

This study was sponsored by Allegro Diagnostics. Dr. Whitney is an employee of the company, and had no other disclosures to report.

ATLANTA – The implantation of nitinol coils that grab and compress diseased lung tissue, thereby allowing for better functioning of healthy tissue, significantly improved quality of life, exercise capacity, and pulmonary lung function in a randomized controlled trial of patients with severe emphysema and hyperinflation.

Specifically, use of the investigational self-actuating, implantable devices in the RESET (Randomized Controlled Trial of RePneu Endobronchial Coils for the Treatment of Severe Emphysema with Hyperinflation) study was associated with a significantly improved mean St. George’s Respiratory Questionnaire score at 90 days after the final treatment in 23 patients who received active treatment, compared with 24 controls who received best medical care.

After adjustment for baseline variables, the between-group difference in the scores was 8.35 points in favor of the treatment group, Dr. Zaid Zoumot reported at the annual meeting of the American College of Chest Physicians.

PneumRx, Inc.

The lung-volume reduction coils also were associated with significant improvements in mean 6-minute walk distance (mean between-group difference of 63.5 m in favor of the treatment group) and forced expiratory volume in 1 second (FEV₁, mean between-group difference of 12% in favor of the treatment group), said Dr. Zoumot of Royal Brompton and Harefield Hospital Trust, London.

The between-group difference in change in mean residual volume did not reach statistical significance, despite a 0.64-L reduction in the treatment group compared with the control group, he noted.

RESET participants were adults with severe emphysema and hyperinflation with significant dyspnea and gas trapping who were screened at three participating centers in the United Kingdom. Those randomized to the treatment group initially underwent implantation of the coils in one lung, with treatment of the contralateral lung after 1 month if appropriate.

Treatment was generally safe and well tolerated; three patients in the treatment group had pneumothoraces, which were picked up on chest x-ray routinely performed 1 hour following the procedure and treated successfully, Dr. Zoumot said. No differences in adverse effects occurred between the groups after the first month of follow-up, including in exacerbations of chronic obstructive pulmonary disorder, he added.

"The safety profile was definitely acceptable, and in fact, the procedures were a lot safer than other endobronchial lung-volume reduction devices at this same stage of development, and certainly a lot safer than lung-volume reduction surgery, which has a quite high morbidity and mortality rate," he said.

The findings are encouraging given the limited therapeutic options for patients with severe emphysema with gas trapping and hyperinflation – particularly those with heterogeneous disease, he said.

Drug therapy is typically of little benefit in these patients, and although lung-volume reduction surgery and endobronchial valve treatment can be helpful in some patients, their use is precluded in many patients, including those with heterogeneous disease in the absence of collateral ventilation, he explained.

The RePneu lung-volume reduction coils, however, provide a minimally invasive mechanical approach to lung-volume reduction that is effective in both homogeneous and heterogeneous emphysema, with benefits unaffected by collateral ventilation, he said. 

The coils, which are made entirely of nitinol – a highly biocompatible "shape memory" material used in numerous implantable devices – are deployed to the lung bronchoscopically using a proprietary delivery system. Initially, the coils are encased in a sheath to allow delivery in a straight configuration, but once they are in place they return to their original coil configuration, gathering and compressing the diseased tissue as they recoil.

The goal is to implant 10 coils per lobe in a fanlike distribution, Dr. Zoumot said. The procedure, which took about 45 minutes on average in this study, is typically performed under conscious sedation, he added.

Patients in the current study will be followed until 12 months after their final treatment, with results reported at both 6 and 12 months. A larger, multicenter randomized controlled trial with longer follow-up is also set to begin recruiting, Dr. Zoumot said.

This study was funded by PneumRx, the maker of the RePneu coils, and the study sites. Dr. Zoumot reported receiving grant funding and payment for travel expenses from PneumRx.

ATLANTA – The implantation of nitinol coils that grab and compress diseased lung tissue, thereby allowing for better functioning of healthy tissue, significantly improved quality of life, exercise capacity, and pulmonary lung function in a randomized controlled trial of patients with severe emphysema and hyperinflation.

Specifically, use of the investigational self-actuating, implantable devices in the RESET (Randomized Controlled Trial of RePneu Endobronchial Coils for the Treatment of Severe Emphysema with Hyperinflation) study was associated with a significantly improved mean St. George’s Respiratory Questionnaire score at 90 days after the final treatment in 23 patients who received active treatment, compared with 24 controls who received best medical care.

After adjustment for baseline variables, the between-group difference in the scores was 8.35 points in favor of the treatment group, Dr. Zaid Zoumot reported at the annual meeting of the American College of Chest Physicians.

PneumRx, Inc.

The lung-volume reduction coils also were associated with significant improvements in mean 6-minute walk distance (mean between-group difference of 63.5 m in favor of the treatment group) and forced expiratory volume in 1 second (FEV₁, mean between-group difference of 12% in favor of the treatment group), said Dr. Zoumot of Royal Brompton and Harefield Hospital Trust, London.

The between-group difference in change in mean residual volume did not reach statistical significance, despite a 0.64-L reduction in the treatment group compared with the control group, he noted.

RESET participants were adults with severe emphysema and hyperinflation with significant dyspnea and gas trapping who were screened at three participating centers in the United Kingdom. Those randomized to the treatment group initially underwent implantation of the coils in one lung, with treatment of the contralateral lung after 1 month if appropriate.

Treatment was generally safe and well tolerated; three patients in the treatment group had pneumothoraces, which were picked up on chest x-ray routinely performed 1 hour following the procedure and treated successfully, Dr. Zoumot said. No differences in adverse effects occurred between the groups after the first month of follow-up, including in exacerbations of chronic obstructive pulmonary disorder, he added.

"The safety profile was definitely acceptable, and in fact, the procedures were a lot safer than other endobronchial lung-volume reduction devices at this same stage of development, and certainly a lot safer than lung-volume reduction surgery, which has a quite high morbidity and mortality rate," he said.

The findings are encouraging given the limited therapeutic options for patients with severe emphysema with gas trapping and hyperinflation – particularly those with heterogeneous disease, he said.

Drug therapy is typically of little benefit in these patients, and although lung-volume reduction surgery and endobronchial valve treatment can be helpful in some patients, their use is precluded in many patients, including those with heterogeneous disease in the absence of collateral ventilation, he explained.

The RePneu lung-volume reduction coils, however, provide a minimally invasive mechanical approach to lung-volume reduction that is effective in both homogeneous and heterogeneous emphysema, with benefits unaffected by collateral ventilation, he said. 

The coils, which are made entirely of nitinol – a highly biocompatible "shape memory" material used in numerous implantable devices – are deployed to the lung bronchoscopically using a proprietary delivery system. Initially, the coils are encased in a sheath to allow delivery in a straight configuration, but once they are in place they return to their original coil configuration, gathering and compressing the diseased tissue as they recoil.

The goal is to implant 10 coils per lobe in a fanlike distribution, Dr. Zoumot said. The procedure, which took about 45 minutes on average in this study, is typically performed under conscious sedation, he added.

Patients in the current study will be followed until 12 months after their final treatment, with results reported at both 6 and 12 months. A larger, multicenter randomized controlled trial with longer follow-up is also set to begin recruiting, Dr. Zoumot said.

This study was funded by PneumRx, the maker of the RePneu coils, and the study sites. Dr. Zoumot reported receiving grant funding and payment for travel expenses from PneumRx.

ATLANTA – The implantation of nitinol coils that grab and compress diseased lung tissue, thereby allowing for better functioning of healthy tissue, significantly improved quality of life, exercise capacity, and pulmonary lung function in a randomized controlled trial of patients with severe emphysema and hyperinflation.

Specifically, use of the investigational self-actuating, implantable devices in the RESET (Randomized Controlled Trial of RePneu Endobronchial Coils for the Treatment of Severe Emphysema with Hyperinflation) study was associated with a significantly improved mean St. George’s Respiratory Questionnaire score at 90 days after the final treatment in 23 patients who received active treatment, compared with 24 controls who received best medical care.

After adjustment for baseline variables, the between-group difference in the scores was 8.35 points in favor of the treatment group, Dr. Zaid Zoumot reported at the annual meeting of the American College of Chest Physicians.

PneumRx, Inc.

The lung-volume reduction coils also were associated with significant improvements in mean 6-minute walk distance (mean between-group difference of 63.5 m in favor of the treatment group) and forced expiratory volume in 1 second (FEV₁, mean between-group difference of 12% in favor of the treatment group), said Dr. Zoumot of Royal Brompton and Harefield Hospital Trust, London.

The between-group difference in change in mean residual volume did not reach statistical significance, despite a 0.64-L reduction in the treatment group compared with the control group, he noted.

RESET participants were adults with severe emphysema and hyperinflation with significant dyspnea and gas trapping who were screened at three participating centers in the United Kingdom. Those randomized to the treatment group initially underwent implantation of the coils in one lung, with treatment of the contralateral lung after 1 month if appropriate.

Treatment was generally safe and well tolerated; three patients in the treatment group had pneumothoraces, which were picked up on chest x-ray routinely performed 1 hour following the procedure and treated successfully, Dr. Zoumot said. No differences in adverse effects occurred between the groups after the first month of follow-up, including in exacerbations of chronic obstructive pulmonary disorder, he added.

"The safety profile was definitely acceptable, and in fact, the procedures were a lot safer than other endobronchial lung-volume reduction devices at this same stage of development, and certainly a lot safer than lung-volume reduction surgery, which has a quite high morbidity and mortality rate," he said.

The findings are encouraging given the limited therapeutic options for patients with severe emphysema with gas trapping and hyperinflation – particularly those with heterogeneous disease, he said.

Drug therapy is typically of little benefit in these patients, and although lung-volume reduction surgery and endobronchial valve treatment can be helpful in some patients, their use is precluded in many patients, including those with heterogeneous disease in the absence of collateral ventilation, he explained.

The RePneu lung-volume reduction coils, however, provide a minimally invasive mechanical approach to lung-volume reduction that is effective in both homogeneous and heterogeneous emphysema, with benefits unaffected by collateral ventilation, he said. 

The coils, which are made entirely of nitinol – a highly biocompatible "shape memory" material used in numerous implantable devices – are deployed to the lung bronchoscopically using a proprietary delivery system. Initially, the coils are encased in a sheath to allow delivery in a straight configuration, but once they are in place they return to their original coil configuration, gathering and compressing the diseased tissue as they recoil.

The goal is to implant 10 coils per lobe in a fanlike distribution, Dr. Zoumot said. The procedure, which took about 45 minutes on average in this study, is typically performed under conscious sedation, he added.

Patients in the current study will be followed until 12 months after their final treatment, with results reported at both 6 and 12 months. A larger, multicenter randomized controlled trial with longer follow-up is also set to begin recruiting, Dr. Zoumot said.

This study was funded by PneumRx, the maker of the RePneu coils, and the study sites. Dr. Zoumot reported receiving grant funding and payment for travel expenses from PneumRx.

ATLANTA – Riociguat, a novel first-in-class soluble guanylate cyclase stimulator, significantly improved 6-minute walk distance in patients with inoperable chronic thromboembolic pulmonary hypertension in the randomized, placebo-controlled phase III CHEST-1 study.

The overall 46-m improvement in 6-minute walk distance at 16 weeks in the study population was largely attributable to improvements in the 173 patients randomized to receive riociguat treatment, as opposed to improvements in 88 patients who received placebo, Dr. Hossein A. Ghofrani reported at the annual meeting of the American College of Chest Physicians.

The improvement in the treatment group was progressive and had not reached a plateau at 16 weeks after treatment initiation. Meanwhile, an initial improvement in the placebo group was followed by a constant decline in the placebo group, said Dr. Ghofrani of University Hospital Giessen and Marburg in Germany.

Treatment also was associated with consistent, significant improvements in a number of secondary end points, including change in pulmonary vascular resistance (PVR), change in World Health Organization functional class, time to clinical worsening, change in Borg dyspnea score, and quality of life assessments, he said.

Hemodynamics were robustly improved, he added, noting that treatment was associated with a 32% reduction in PVR, which translated into a highly significant 246-dyne reduction.

Patients enrolled in the multicenter CHEST-1 study – the largest placebo-controlled study to date of chronic thromboembolic pulmonary hypertension (CTEPH), for which there are currently no approved medical treatments – were aged 18-80 years with either inoperable disease or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. They had a mean PVR of greater than 480 dyn.s/cm⁵.

Treatment with riociguat was initiated at an oral dose of 1 mg three times daily titrated up to a maximum of 2.5 mg three times daily as tolerated according to systolic blood pressure; 90% achieved the highest dose, attesting to the tolerability of the drug, Dr. Ghofrani said.

In fact, the adverse event rate was very low, and side effects were similar to those seen in the PATENT-1 trial of riociguat for pulmonary arterial hypertension (PAH), which also was reported at the meeting.

These included headache, dizziness, peripheral edema (which occurred more often in the placebo group), cough, dyspnea, nasopharyngitis, nausea, diarrhea, and vomiting.

The findings are encouraging given the lack of medical treatments for CETPH patients who either are ineligible for surgical treatment or have persistent pulmonary hypertension after surgery, Dr. Ghofrani said.

The study of riociguat for CETPH is ongoing. CHEST-1 completers were allowed to enroll in a long-term extension study (CHEST-2), and results of that study will be reported next year, Dr. Ghofrani said.

As for how it is that a single molecule appears to have efficacy for two distinct pulmonary hypertension subgroups (PAH and CETPH), which are believed to have differing pathophysiological mechanisms, he explained that the disease might have some "common denominators."

"After a certain level of severity, they have a lot of commonalities, and the progressive component, for instance for pulmonary vascular remodeling beyond a certain point of no return, becomes very much alike in the different disease entities. The lack of the endogenous [nitric oxide] signaling pathway has been proven for many of these diseases. ... I think there may be a common denominator for the disease, even if the underlying pathophysiology may be different," he explained.

This is not to say riociguat is a "magic bullet" for all pulmonary hypertension subgroups, he added.

The drug’s efficacy "has to be proven in each single indication with a proper randomized controlled trial," he said.

In addition to the PATENT-1 and CHEST-1 studies showing efficacy in PAH and CETPH, respectively, studies of other pulmonary hypertension disease subgroups are underway, including one involving patients with left heart systolic disorders and PAH; phase II data from that study will be presented at an upcoming meeting of the American Heart Association, he said.

The PATENT and CHEST trials are supported by Bayer, the maker of riociguat. Dr. Ghofrani disclosed that he has received grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and German Ministry for Education and Research; and from Bayer HealthCare, Aires, and other companies. He also has received payment for consulting and serving on speakers bureaus or advisory committees of several pharmaceutical companies.

ATLANTA – Riociguat, a novel first-in-class soluble guanylate cyclase stimulator, significantly improved 6-minute walk distance in patients with inoperable chronic thromboembolic pulmonary hypertension in the randomized, placebo-controlled phase III CHEST-1 study.

The overall 46-m improvement in 6-minute walk distance at 16 weeks in the study population was largely attributable to improvements in the 173 patients randomized to receive riociguat treatment, as opposed to improvements in 88 patients who received placebo, Dr. Hossein A. Ghofrani reported at the annual meeting of the American College of Chest Physicians.

The improvement in the treatment group was progressive and had not reached a plateau at 16 weeks after treatment initiation. Meanwhile, an initial improvement in the placebo group was followed by a constant decline in the placebo group, said Dr. Ghofrani of University Hospital Giessen and Marburg in Germany.

Treatment also was associated with consistent, significant improvements in a number of secondary end points, including change in pulmonary vascular resistance (PVR), change in World Health Organization functional class, time to clinical worsening, change in Borg dyspnea score, and quality of life assessments, he said.

Hemodynamics were robustly improved, he added, noting that treatment was associated with a 32% reduction in PVR, which translated into a highly significant 246-dyne reduction.

Patients enrolled in the multicenter CHEST-1 study – the largest placebo-controlled study to date of chronic thromboembolic pulmonary hypertension (CTEPH), for which there are currently no approved medical treatments – were aged 18-80 years with either inoperable disease or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. They had a mean PVR of greater than 480 dyn.s/cm⁵.

Treatment with riociguat was initiated at an oral dose of 1 mg three times daily titrated up to a maximum of 2.5 mg three times daily as tolerated according to systolic blood pressure; 90% achieved the highest dose, attesting to the tolerability of the drug, Dr. Ghofrani said.

In fact, the adverse event rate was very low, and side effects were similar to those seen in the PATENT-1 trial of riociguat for pulmonary arterial hypertension (PAH), which also was reported at the meeting.

These included headache, dizziness, peripheral edema (which occurred more often in the placebo group), cough, dyspnea, nasopharyngitis, nausea, diarrhea, and vomiting.

The findings are encouraging given the lack of medical treatments for CETPH patients who either are ineligible for surgical treatment or have persistent pulmonary hypertension after surgery, Dr. Ghofrani said.

The study of riociguat for CETPH is ongoing. CHEST-1 completers were allowed to enroll in a long-term extension study (CHEST-2), and results of that study will be reported next year, Dr. Ghofrani said.

As for how it is that a single molecule appears to have efficacy for two distinct pulmonary hypertension subgroups (PAH and CETPH), which are believed to have differing pathophysiological mechanisms, he explained that the disease might have some "common denominators."

"After a certain level of severity, they have a lot of commonalities, and the progressive component, for instance for pulmonary vascular remodeling beyond a certain point of no return, becomes very much alike in the different disease entities. The lack of the endogenous [nitric oxide] signaling pathway has been proven for many of these diseases. ... I think there may be a common denominator for the disease, even if the underlying pathophysiology may be different," he explained.

This is not to say riociguat is a "magic bullet" for all pulmonary hypertension subgroups, he added.

The drug’s efficacy "has to be proven in each single indication with a proper randomized controlled trial," he said.

In addition to the PATENT-1 and CHEST-1 studies showing efficacy in PAH and CETPH, respectively, studies of other pulmonary hypertension disease subgroups are underway, including one involving patients with left heart systolic disorders and PAH; phase II data from that study will be presented at an upcoming meeting of the American Heart Association, he said.

The PATENT and CHEST trials are supported by Bayer, the maker of riociguat. Dr. Ghofrani disclosed that he has received grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and German Ministry for Education and Research; and from Bayer HealthCare, Aires, and other companies. He also has received payment for consulting and serving on speakers bureaus or advisory committees of several pharmaceutical companies.

ATLANTA – Riociguat, a novel first-in-class soluble guanylate cyclase stimulator, significantly improved 6-minute walk distance in patients with inoperable chronic thromboembolic pulmonary hypertension in the randomized, placebo-controlled phase III CHEST-1 study.

The overall 46-m improvement in 6-minute walk distance at 16 weeks in the study population was largely attributable to improvements in the 173 patients randomized to receive riociguat treatment, as opposed to improvements in 88 patients who received placebo, Dr. Hossein A. Ghofrani reported at the annual meeting of the American College of Chest Physicians.

The improvement in the treatment group was progressive and had not reached a plateau at 16 weeks after treatment initiation. Meanwhile, an initial improvement in the placebo group was followed by a constant decline in the placebo group, said Dr. Ghofrani of University Hospital Giessen and Marburg in Germany.

Treatment also was associated with consistent, significant improvements in a number of secondary end points, including change in pulmonary vascular resistance (PVR), change in World Health Organization functional class, time to clinical worsening, change in Borg dyspnea score, and quality of life assessments, he said.

Hemodynamics were robustly improved, he added, noting that treatment was associated with a 32% reduction in PVR, which translated into a highly significant 246-dyne reduction.

Patients enrolled in the multicenter CHEST-1 study – the largest placebo-controlled study to date of chronic thromboembolic pulmonary hypertension (CTEPH), for which there are currently no approved medical treatments – were aged 18-80 years with either inoperable disease or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. They had a mean PVR of greater than 480 dyn.s/cm⁵.

Treatment with riociguat was initiated at an oral dose of 1 mg three times daily titrated up to a maximum of 2.5 mg three times daily as tolerated according to systolic blood pressure; 90% achieved the highest dose, attesting to the tolerability of the drug, Dr. Ghofrani said.

In fact, the adverse event rate was very low, and side effects were similar to those seen in the PATENT-1 trial of riociguat for pulmonary arterial hypertension (PAH), which also was reported at the meeting.

These included headache, dizziness, peripheral edema (which occurred more often in the placebo group), cough, dyspnea, nasopharyngitis, nausea, diarrhea, and vomiting.

The findings are encouraging given the lack of medical treatments for CETPH patients who either are ineligible for surgical treatment or have persistent pulmonary hypertension after surgery, Dr. Ghofrani said.

The study of riociguat for CETPH is ongoing. CHEST-1 completers were allowed to enroll in a long-term extension study (CHEST-2), and results of that study will be reported next year, Dr. Ghofrani said.

As for how it is that a single molecule appears to have efficacy for two distinct pulmonary hypertension subgroups (PAH and CETPH), which are believed to have differing pathophysiological mechanisms, he explained that the disease might have some "common denominators."

"After a certain level of severity, they have a lot of commonalities, and the progressive component, for instance for pulmonary vascular remodeling beyond a certain point of no return, becomes very much alike in the different disease entities. The lack of the endogenous [nitric oxide] signaling pathway has been proven for many of these diseases. ... I think there may be a common denominator for the disease, even if the underlying pathophysiology may be different," he explained.

This is not to say riociguat is a "magic bullet" for all pulmonary hypertension subgroups, he added.

The drug’s efficacy "has to be proven in each single indication with a proper randomized controlled trial," he said.

In addition to the PATENT-1 and CHEST-1 studies showing efficacy in PAH and CETPH, respectively, studies of other pulmonary hypertension disease subgroups are underway, including one involving patients with left heart systolic disorders and PAH; phase II data from that study will be presented at an upcoming meeting of the American Heart Association, he said.

The PATENT and CHEST trials are supported by Bayer, the maker of riociguat. Dr. Ghofrani disclosed that he has received grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and German Ministry for Education and Research; and from Bayer HealthCare, Aires, and other companies. He also has received payment for consulting and serving on speakers bureaus or advisory committees of several pharmaceutical companies.