Debra L. Beck

 

TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.

While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.

Debra Beck/Frontline Medical News

“These data deal with a topic that we scratch our heads about all the time – the asthma COPD overlap. … Few of our therapies for asthma have been studied in this patient population,” said Nicola Hanania, MD, FCCP, of Baylor College of Medicine in Houston. “We believe that about 16% of patients with asthma or COPD have ACO,” he added.

Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).

Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.

“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported. Specifically, asthma exacerbations numbers were reduced from baseline levels though month 12, from 3 or more exacerbations in both ACO and non ACO groups to 1.1 or less.

Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.

Postbronchodilator FEV₁ at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV₁ was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.

Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.

Adverse events were consistent with the known safety profile of omalizumab.

“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.

Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.

 

TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.

While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.

Debra Beck/Frontline Medical News

“These data deal with a topic that we scratch our heads about all the time – the asthma COPD overlap. … Few of our therapies for asthma have been studied in this patient population,” said Nicola Hanania, MD, FCCP, of Baylor College of Medicine in Houston. “We believe that about 16% of patients with asthma or COPD have ACO,” he added.

Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).

Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.

“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported. Specifically, asthma exacerbations numbers were reduced from baseline levels though month 12, from 3 or more exacerbations in both ACO and non ACO groups to 1.1 or less.

Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.

Postbronchodilator FEV₁ at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV₁ was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.

Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.

Adverse events were consistent with the known safety profile of omalizumab.

“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.

Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.

 

TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.

While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.

Debra Beck/Frontline Medical News

“These data deal with a topic that we scratch our heads about all the time – the asthma COPD overlap. … Few of our therapies for asthma have been studied in this patient population,” said Nicola Hanania, MD, FCCP, of Baylor College of Medicine in Houston. “We believe that about 16% of patients with asthma or COPD have ACO,” he added.

Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).

Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.

“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported. Specifically, asthma exacerbations numbers were reduced from baseline levels though month 12, from 3 or more exacerbations in both ACO and non ACO groups to 1.1 or less.

Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.

Postbronchodilator FEV₁ at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV₁ was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.

Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.

Adverse events were consistent with the known safety profile of omalizumab.

“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.

Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.

 

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

“These results are certainly reassuring from the safety perspective and confirm previously published shorter-term efficacy and safety studies with this medication,” reported Nicola A. Hanania, MD, FCCP, from Baylor College of Medicine, Houston.

The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.

This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV_1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.

Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.

Formoterol significantly improved trough forced expiratory volume in 1 second (FEV₁), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.

Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.

In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”

The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.

Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.

 

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

“These results are certainly reassuring from the safety perspective and confirm previously published shorter-term efficacy and safety studies with this medication,” reported Nicola A. Hanania, MD, FCCP, from Baylor College of Medicine, Houston.

The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.

This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV_1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.

Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.

Formoterol significantly improved trough forced expiratory volume in 1 second (FEV₁), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.

Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.

In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”

The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.

Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.

 

TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.

Debra L. Beck/Frontline Medical News

“These results are certainly reassuring from the safety perspective and confirm previously published shorter-term efficacy and safety studies with this medication,” reported Nicola A. Hanania, MD, FCCP, from Baylor College of Medicine, Houston.

The Food and Drug Administration approved formoterol fumarate, a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.

This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV_1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.

Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.

Formoterol significantly improved trough forced expiratory volume in 1 second (FEV₁), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.

Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly tiotropium, reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.

In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”

The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. Am J Respir Crit Care Med. 2017;195 A5473 [abstract]), while the lung function data are new, said Dr. Hanania.

Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.

 

TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*

There are currently no nebulized LAMAs approved for use in the U.S.

Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.

Debra Beck/Frontline Medical News

“Glycopyrrolate works,” reported Dr. Ohar. “It improves FEV1 [at week 12], not only in the statistically significant manner but in a clinically significant manner, both at the 25-microgram and 50-microgram dose…And when you cut the data according to FEV1, you again see a statistically significant improvement regardless [of whether] your FEV1 at baseline was less than 50% of predicted versus greater than or equal to 50%.”

Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.

Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.

The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.

Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.

“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.

GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.

Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.

Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.

*This article was updated on Nov. 6, 2017.
 

 

TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*

There are currently no nebulized LAMAs approved for use in the U.S.

Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.

Debra Beck/Frontline Medical News

“Glycopyrrolate works,” reported Dr. Ohar. “It improves FEV1 [at week 12], not only in the statistically significant manner but in a clinically significant manner, both at the 25-microgram and 50-microgram dose…And when you cut the data according to FEV1, you again see a statistically significant improvement regardless [of whether] your FEV1 at baseline was less than 50% of predicted versus greater than or equal to 50%.”

Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.

Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.

The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.

Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.

“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.

GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.

Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.

Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.

*This article was updated on Nov. 6, 2017.
 

 

TORONTO – Glycopyrrolate, a novel nebulized long-acting muscarinic antagonist (LAMA) in development, was well-tolerated and significantly improved lung function and health status in COPD patients regardless of baseline lung function or age, according to a subgroup analysis of pooled results from two randomized trials.*

There are currently no nebulized LAMAs approved for use in the U.S.

Jill Ohar, MD, from Wake Forest University School of Medicine (Winston-Salem, N.C.), presented this secondary analysis of the GOLDEN-3 and GOLDEN-4 trials at the CHEST annual meeting. She and her colleagues evaluated the efficacy and safety of glycopyrrolate in patients with a forced expiratory volume 1(FEV1) % predicted of less than 50 and an FEV1 % predicted of greater than or equal to 50, in age ranges of less than 65 years, greater than or equal to 65 years and at least 75 years, as measured by trough FEV1.

Debra Beck/Frontline Medical News

“Glycopyrrolate works,” reported Dr. Ohar. “It improves FEV1 [at week 12], not only in the statistically significant manner but in a clinically significant manner, both at the 25-microgram and 50-microgram dose…And when you cut the data according to FEV1, you again see a statistically significant improvement regardless [of whether] your FEV1 at baseline was less than 50% of predicted versus greater than or equal to 50%.”

Similarly, both glycopyrrolate doses produced significant (P less than .05) and clinically meaningful lung function improvements vs. placebo in participants less than 65 years of age, at least 65 years, and greater than or equal to 75 years.

Glycopyrrolate use for 12 weeks led to greater improvements over placebo in St. George’s Respiratory Questionnaire (SGRQ) total score, in patients in both lung function classes. There were a higher percentage of SGRQ responders in the treatment arms compared to placebo arms.

The highest SGRQ improvement in SGRQ (−6.287) was seen in the 47 patients that comprised the at-least-75 years of age subgroup receiving glycopyrrolate 25 mcg BID. “It’s a small number of people, but I think it’s [valuable] to see if the very aged act in any way differently than the entire greater than or equal to 65-year-old group,” said Dr. Ohar.

Adverse event rates were similar for placebo and both glycopyrrolate doses, with no safety signals seen according to baseline lung function or age. Few cardiovascular events of special interest were seen.

“Looking at major adverse cardiovascular events, such as fatal MIs, other cardiovascular deaths, arrhythmias, etc., we see nothing that would suggest that the drug overall is associated with an undue number of these versus placebo,” reported Dr. Ohar.

GOLDEN 3 and 4 were replicate, 12-week, phase 3, randomized, double-blind, placebo-controlled studies that evaluated glycopyrrolate solution administered by an investigational eFlow Close System (eFLOW CS) nebulizer in individuals with moderate-to-very severe COPD, including those with continued background use of a long-acting beta2-agonist (LABA), with or without an inhaled corticosteroid (ICS). In each of the trials, about 30% of patients were on LABA ICS, noted Dr. Ohar in her presentation. A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4.

Its manufacturer, Sunovion Pharmaceuticals, resubmitted the product to the FDA in June 2017 in response to a Complete Response Letter received from the FDA in May 2017. The FDA is expected to act on the new submission on December 15, 2017. The novel agent is being considered for the long-term, maintenance treatment of airflow obstruction in people with COPD, including chronic bronchitis and/or emphysema.

Dr. Ohar reported that she serves on the advisory boards of several pharmaceutical companies. The other three authors are employees of Sunovion Pharmaceuticals Inc.

*This article was updated on Nov. 6, 2017.
 

 

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

“Epidemiological models have indicated that in order to eliminate the threat of TB in the United States, it will require a strategy of targeting latent tuberculosis infection specifically among foreign-born individuals,” he said during his presentation. “This highlights the need for us practitioners on the front line to have sound knowledge of identification, screening, and management of latent TB infection, especially given the multiple modalities for diagnosis.”

Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.

While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.

Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.

Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”

Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.

One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.

To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.

“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”

The authors reported there were no product or funding disclosures relevant to this study.

 

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

“Epidemiological models have indicated that in order to eliminate the threat of TB in the United States, it will require a strategy of targeting latent tuberculosis infection specifically among foreign-born individuals,” he said during his presentation. “This highlights the need for us practitioners on the front line to have sound knowledge of identification, screening, and management of latent TB infection, especially given the multiple modalities for diagnosis.”

Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.

While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.

Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.

Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”

Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.

One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.

To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.

“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”

The authors reported there were no product or funding disclosures relevant to this study.

 

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

“Epidemiological models have indicated that in order to eliminate the threat of TB in the United States, it will require a strategy of targeting latent tuberculosis infection specifically among foreign-born individuals,” he said during his presentation. “This highlights the need for us practitioners on the front line to have sound knowledge of identification, screening, and management of latent TB infection, especially given the multiple modalities for diagnosis.”

Among 304 clinicians who responded to an invitation to an online questionnaire, 78% said they preferred to use IGRA over TST and 91% said they had a “good understanding” of how to use and interpret IGRA. However, when queried further on how to best use and interpret IGRAs according to current guidelines, their answers to 11 knowledge-based questions told a somewhat different story, said Dr. Green, who is an intensivist at Cooper University Health Care in Camden, N.J.

While 96% knew IGRAs are not helpful in monitoring response to TB treatment, 20% erroneously thought that a positive IGRA predicts latent TB infection reactivation in the future.

Most respondents correctly answered two “fundamental” questions on cross-reactivity of IGRAs with Mycobacterium avium complex and bacilli Calmette-Guérin (BCG) vaccination (84% and 96%, respectively). “While 80% sounds good, I think we’re talking about ID and pulmonary docs at the best institutions across the United States, so I would have expected much higher,” Dr. Green said.

Only one-third of respondents knew that the T-SPOT.TB test, an IGRA, had the highest sensitivity for identifying those with latent TB infection. And only about half were able to appropriately identify the need to initiate therapy for latent TB in a scenario in which the patient was at “high risk for latent tuberculosis with a positive tuberculin skin test and a negative interferon-gamma release assay.”

Fellows comprised 42.5% of respondents and the remainder were attendings of varying levels of seniority. About half of respondents were pulmonologists and the other half infectious disease specialists. The majority (91%) were practicing or training in university hospitals.

One major limitation of the study, said Dr. Green, is the low response rate. “I would have liked 3,000 responses,” he said, rather than just over 300.

To disseminate the questionnaire, he contacted pulmonary and infectious disease academic program directors and coordinators and asked them to forward the survey invitation to their full-time faculty and fellows. Dr. Green also acknowledged that his project missed those physicians not working in academic centers.

“I would like to think that the reason people didn’t do as well as I had hoped is because of the conflicting literature out there and using not necessarily the guidelines but rather their current knowledge on what was most recently published,” said Dr. Green. “But maybe there is a true misunderstanding.”

The authors reported there were no product or funding disclosures relevant to this study.

 

TORONTO – Extracorporeal membrane oxygenation (ECMO) is associated with lung recovery rates as high as 90% in pediatric patients with near-fatal asthma, but the risk of complications was also high and the cannulation technique employed made a significant difference to outcomes, according to a study presented at the CHEST annual meeting.

“ECMO for near-fatal asthma is a potentially life-saving intervention, however, clinicians should be aware of the potentially severe complications, particularly with veno-arterial cannulation in this population,” said Rebecca Kohlberg-Davis, MD, a pediatric resident at Connecticut Children’s Medical Center, Hartford.

Debra L. Beck/Frontline Medical News

ECMO is being used increasingly in the setting of near-fatal pediatric asthma but there are limited data on outcomes in this population. Dr. Kohlberg-Davis and her colleagues conducted a retrospective analysis of all children with asthma who were treated with ECMO using the Extracorporeal Life Support Organization (ELSO) registry.

Between 1988 and 2016, 371 children with status asthmaticus underwent ECMO cannulation using one of two methods. Sixty-five percent were treated with ECMO using veno-venous (VV) cannulation and 33% were treated using veno-arterial (VA) cannulation. Both VV and VA require insertion of a cannula to take deoxygenated blood from a central vein or the right atrium. VA ECMO returns the oxygenated blood, under pressure, to the arterial side of the circulation (typically to the aorta), supporting cardiac output, while VV ECMO returns oxygenated blood back to a large vein and does not support circulation.

The median age of the study participants was 7.5 years and 56% were male. The median ECMO run duration was 123 hours.

Overall, lung recovery was seen in 83% of patients, and 77% were discharged from the hospital. Of the children who received VV cannulation, 90% experienced lung recovery, while VA cannulation was associated with only a 69% rate of lung recovery and significantly more complications. Among those who experienced lung recovery, those who received VV cannulation had a 3.6-fold higher likelihood of survival (P = .006), Dr. Kohlberg-Davis reported.

At presentation, 88% of patients had hypercarbic respiratory failure, 34% had hypoxemic respiratory failure, and 27% had mixed respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxemic or combined respiratory failure were more likely to receive VA cannulation. Those with hypoxemic respiratory failure had a significantly lower likelihood of lung recovery (odds ratio, 4.9; P less than .0001), she said.

Eighty percent of runs were associated with one or more complications and 20% had three or more complications. Of that 80%, most involved cardiovascular complications (53%), while 36% were hemorrhagic and 35% were mechanical. The most common cardiovascular complications included the need for inotropic support (in 39% of patients) and hypertension requiring vasodilators (in 18% of patients). The most common hemorrhagic complications were cannula-site bleeding (23%) and surgical-site bleeding (8%), while mechanical complications were mostly clots (19%) and cannulation problems (12%).

Children who received VA cannulation had a significantly higher rate of neurologic complications, compared with those who received VV cannulation (22% vs. 5%), and these included cerebral hemorrhage or infarct in 6% and clinical brain death in 5%.

“If early cannulation with VV ECMO could prevent the need for VA ECMO, this might lead to lower neurological complication and increased survival,” said Dr. Kohlberg-Davis. Current guidelines recommend considering cannulation at an oxygenation index – used to measure the fraction of inspired oxygen and its usage within the body – between 40 and 60. This study suggests that initiating cannulation at a lower OI is associated with better outcomes and fewer complications, she said.

The authors reported having nothing to disclose.

 

TORONTO – Extracorporeal membrane oxygenation (ECMO) is associated with lung recovery rates as high as 90% in pediatric patients with near-fatal asthma, but the risk of complications was also high and the cannulation technique employed made a significant difference to outcomes, according to a study presented at the CHEST annual meeting.

“ECMO for near-fatal asthma is a potentially life-saving intervention, however, clinicians should be aware of the potentially severe complications, particularly with veno-arterial cannulation in this population,” said Rebecca Kohlberg-Davis, MD, a pediatric resident at Connecticut Children’s Medical Center, Hartford.

Debra L. Beck/Frontline Medical News

ECMO is being used increasingly in the setting of near-fatal pediatric asthma but there are limited data on outcomes in this population. Dr. Kohlberg-Davis and her colleagues conducted a retrospective analysis of all children with asthma who were treated with ECMO using the Extracorporeal Life Support Organization (ELSO) registry.

Between 1988 and 2016, 371 children with status asthmaticus underwent ECMO cannulation using one of two methods. Sixty-five percent were treated with ECMO using veno-venous (VV) cannulation and 33% were treated using veno-arterial (VA) cannulation. Both VV and VA require insertion of a cannula to take deoxygenated blood from a central vein or the right atrium. VA ECMO returns the oxygenated blood, under pressure, to the arterial side of the circulation (typically to the aorta), supporting cardiac output, while VV ECMO returns oxygenated blood back to a large vein and does not support circulation.

The median age of the study participants was 7.5 years and 56% were male. The median ECMO run duration was 123 hours.

Overall, lung recovery was seen in 83% of patients, and 77% were discharged from the hospital. Of the children who received VV cannulation, 90% experienced lung recovery, while VA cannulation was associated with only a 69% rate of lung recovery and significantly more complications. Among those who experienced lung recovery, those who received VV cannulation had a 3.6-fold higher likelihood of survival (P = .006), Dr. Kohlberg-Davis reported.

At presentation, 88% of patients had hypercarbic respiratory failure, 34% had hypoxemic respiratory failure, and 27% had mixed respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxemic or combined respiratory failure were more likely to receive VA cannulation. Those with hypoxemic respiratory failure had a significantly lower likelihood of lung recovery (odds ratio, 4.9; P less than .0001), she said.

Eighty percent of runs were associated with one or more complications and 20% had three or more complications. Of that 80%, most involved cardiovascular complications (53%), while 36% were hemorrhagic and 35% were mechanical. The most common cardiovascular complications included the need for inotropic support (in 39% of patients) and hypertension requiring vasodilators (in 18% of patients). The most common hemorrhagic complications were cannula-site bleeding (23%) and surgical-site bleeding (8%), while mechanical complications were mostly clots (19%) and cannulation problems (12%).

Children who received VA cannulation had a significantly higher rate of neurologic complications, compared with those who received VV cannulation (22% vs. 5%), and these included cerebral hemorrhage or infarct in 6% and clinical brain death in 5%.

“If early cannulation with VV ECMO could prevent the need for VA ECMO, this might lead to lower neurological complication and increased survival,” said Dr. Kohlberg-Davis. Current guidelines recommend considering cannulation at an oxygenation index – used to measure the fraction of inspired oxygen and its usage within the body – between 40 and 60. This study suggests that initiating cannulation at a lower OI is associated with better outcomes and fewer complications, she said.

The authors reported having nothing to disclose.

 

TORONTO – Extracorporeal membrane oxygenation (ECMO) is associated with lung recovery rates as high as 90% in pediatric patients with near-fatal asthma, but the risk of complications was also high and the cannulation technique employed made a significant difference to outcomes, according to a study presented at the CHEST annual meeting.

“ECMO for near-fatal asthma is a potentially life-saving intervention, however, clinicians should be aware of the potentially severe complications, particularly with veno-arterial cannulation in this population,” said Rebecca Kohlberg-Davis, MD, a pediatric resident at Connecticut Children’s Medical Center, Hartford.

Debra L. Beck/Frontline Medical News

ECMO is being used increasingly in the setting of near-fatal pediatric asthma but there are limited data on outcomes in this population. Dr. Kohlberg-Davis and her colleagues conducted a retrospective analysis of all children with asthma who were treated with ECMO using the Extracorporeal Life Support Organization (ELSO) registry.

Between 1988 and 2016, 371 children with status asthmaticus underwent ECMO cannulation using one of two methods. Sixty-five percent were treated with ECMO using veno-venous (VV) cannulation and 33% were treated using veno-arterial (VA) cannulation. Both VV and VA require insertion of a cannula to take deoxygenated blood from a central vein or the right atrium. VA ECMO returns the oxygenated blood, under pressure, to the arterial side of the circulation (typically to the aorta), supporting cardiac output, while VV ECMO returns oxygenated blood back to a large vein and does not support circulation.

The median age of the study participants was 7.5 years and 56% were male. The median ECMO run duration was 123 hours.

Overall, lung recovery was seen in 83% of patients, and 77% were discharged from the hospital. Of the children who received VV cannulation, 90% experienced lung recovery, while VA cannulation was associated with only a 69% rate of lung recovery and significantly more complications. Among those who experienced lung recovery, those who received VV cannulation had a 3.6-fold higher likelihood of survival (P = .006), Dr. Kohlberg-Davis reported.

At presentation, 88% of patients had hypercarbic respiratory failure, 34% had hypoxemic respiratory failure, and 27% had mixed respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxemic or combined respiratory failure were more likely to receive VA cannulation. Those with hypoxemic respiratory failure had a significantly lower likelihood of lung recovery (odds ratio, 4.9; P less than .0001), she said.

Eighty percent of runs were associated with one or more complications and 20% had three or more complications. Of that 80%, most involved cardiovascular complications (53%), while 36% were hemorrhagic and 35% were mechanical. The most common cardiovascular complications included the need for inotropic support (in 39% of patients) and hypertension requiring vasodilators (in 18% of patients). The most common hemorrhagic complications were cannula-site bleeding (23%) and surgical-site bleeding (8%), while mechanical complications were mostly clots (19%) and cannulation problems (12%).

Children who received VA cannulation had a significantly higher rate of neurologic complications, compared with those who received VV cannulation (22% vs. 5%), and these included cerebral hemorrhage or infarct in 6% and clinical brain death in 5%.

“If early cannulation with VV ECMO could prevent the need for VA ECMO, this might lead to lower neurological complication and increased survival,” said Dr. Kohlberg-Davis. Current guidelines recommend considering cannulation at an oxygenation index – used to measure the fraction of inspired oxygen and its usage within the body – between 40 and 60. This study suggests that initiating cannulation at a lower OI is associated with better outcomes and fewer complications, she said.

The authors reported having nothing to disclose.

 

TORONTO – Patients who received an influenza vaccination but still required hospitalization for H1N1 influenza had better outcomes, compared with unvaccinated patients, according to findings from a retrospective study.

In the hospital, vaccinated patients had significantly lower rates of acute kidney injury (6% vs. 35%; P = .038) and were more likely to be satisfactorily managed with noninvasive mechanical ventilation (41% vs. 6%; P = .004).

Debra Beck/ Frontline Medical News

“Even though the vaccine is effective, it’s not completely effective in preventing the illness,” said Twinkle Chandak, MD, a pulmonologist at the Berkshire Medical Center in Pittsfield, Mass., who presented the study at the CHEST annual meeting. The Centers for Disease Control and Prevention reported that 2015-2016 vaccination effectiveness was about 41%, she noted.

Dr. Chandak and her colleagues studied 72 cases of seasonal influenza requiring hospitalization from September 2015 to April 2016 at Berkshire Medical Center, a 300-bed teaching hospital in western Massachusetts. Based on rapid polymerase chain reaction testing, 51 of these patients were positive for H1N1, of which 38 had received a seasonal flu vaccine.

H1N1 patients who had received vaccination were significantly older (70.4 years vs. 59.6 years; P = .016) and were more often smokers (76% vs. 38%; P = .017), compared with patients who were unvaccinated.

The finding that the unvaccinated patients were younger and still had poorer outcomes, “emphasizes the need for widespread vaccination,” Dr. Chandak said.

There were several parameters that trended in favor of vaccination, but did not reach statistical significance due to the relatively small sample size, Dr. Chandak said. These included a trend towards more ICU admission in the unvaccinated, compared with vaccinated patients (21% and 12%, respectively; P = .699), a longer ICU stay (1.7 days and 0.2 days; P = .144), more multiorgan dysfunction syndrome (12% and 6%; P = .654), and more acute respiratory distress syndrome (6% and 0%; P = .547). Vasopressors were needed in a similar proportion of patients (12% of both groups).

During the 2009-2010 flu season, H1N1 was the cause of about 61 million cases of influenza in the United States, 274,000 hospitalizations, and 12,470 deaths, Dr. Chandak reported.

Since the 2010-2011 influenza season, the trivalent influenza vaccine has included antigen from the 2009 pandemic H1N1 influenza A virus. This has prevented between 700,000 and 1.5 million cases of H1N1, up to 10,000 hospitalizations, and as many as 500 deaths, according to surveillance data (Emerg Infect Dis. 2013;19[3]:439-48).

The viral subtype made a strong reappearance in the 2015-2016 flu season when it was again the predominant viral subtype of the season, according to the CDC. Most studies have looked at the effectiveness of the vaccine, but have not studied critical care outcomes in vaccinated versus unvaccinated patients, Dr. Chandak noted.

Dr. Chandak reported having no financial disclosures.

 

TORONTO – Patients who received an influenza vaccination but still required hospitalization for H1N1 influenza had better outcomes, compared with unvaccinated patients, according to findings from a retrospective study.

In the hospital, vaccinated patients had significantly lower rates of acute kidney injury (6% vs. 35%; P = .038) and were more likely to be satisfactorily managed with noninvasive mechanical ventilation (41% vs. 6%; P = .004).

Debra Beck/ Frontline Medical News

“Even though the vaccine is effective, it’s not completely effective in preventing the illness,” said Twinkle Chandak, MD, a pulmonologist at the Berkshire Medical Center in Pittsfield, Mass., who presented the study at the CHEST annual meeting. The Centers for Disease Control and Prevention reported that 2015-2016 vaccination effectiveness was about 41%, she noted.

Dr. Chandak and her colleagues studied 72 cases of seasonal influenza requiring hospitalization from September 2015 to April 2016 at Berkshire Medical Center, a 300-bed teaching hospital in western Massachusetts. Based on rapid polymerase chain reaction testing, 51 of these patients were positive for H1N1, of which 38 had received a seasonal flu vaccine.

H1N1 patients who had received vaccination were significantly older (70.4 years vs. 59.6 years; P = .016) and were more often smokers (76% vs. 38%; P = .017), compared with patients who were unvaccinated.

The finding that the unvaccinated patients were younger and still had poorer outcomes, “emphasizes the need for widespread vaccination,” Dr. Chandak said.

There were several parameters that trended in favor of vaccination, but did not reach statistical significance due to the relatively small sample size, Dr. Chandak said. These included a trend towards more ICU admission in the unvaccinated, compared with vaccinated patients (21% and 12%, respectively; P = .699), a longer ICU stay (1.7 days and 0.2 days; P = .144), more multiorgan dysfunction syndrome (12% and 6%; P = .654), and more acute respiratory distress syndrome (6% and 0%; P = .547). Vasopressors were needed in a similar proportion of patients (12% of both groups).

During the 2009-2010 flu season, H1N1 was the cause of about 61 million cases of influenza in the United States, 274,000 hospitalizations, and 12,470 deaths, Dr. Chandak reported.

Since the 2010-2011 influenza season, the trivalent influenza vaccine has included antigen from the 2009 pandemic H1N1 influenza A virus. This has prevented between 700,000 and 1.5 million cases of H1N1, up to 10,000 hospitalizations, and as many as 500 deaths, according to surveillance data (Emerg Infect Dis. 2013;19[3]:439-48).

The viral subtype made a strong reappearance in the 2015-2016 flu season when it was again the predominant viral subtype of the season, according to the CDC. Most studies have looked at the effectiveness of the vaccine, but have not studied critical care outcomes in vaccinated versus unvaccinated patients, Dr. Chandak noted.

Dr. Chandak reported having no financial disclosures.

 

TORONTO – Patients who received an influenza vaccination but still required hospitalization for H1N1 influenza had better outcomes, compared with unvaccinated patients, according to findings from a retrospective study.

In the hospital, vaccinated patients had significantly lower rates of acute kidney injury (6% vs. 35%; P = .038) and were more likely to be satisfactorily managed with noninvasive mechanical ventilation (41% vs. 6%; P = .004).

Debra Beck/ Frontline Medical News

“Even though the vaccine is effective, it’s not completely effective in preventing the illness,” said Twinkle Chandak, MD, a pulmonologist at the Berkshire Medical Center in Pittsfield, Mass., who presented the study at the CHEST annual meeting. The Centers for Disease Control and Prevention reported that 2015-2016 vaccination effectiveness was about 41%, she noted.

Dr. Chandak and her colleagues studied 72 cases of seasonal influenza requiring hospitalization from September 2015 to April 2016 at Berkshire Medical Center, a 300-bed teaching hospital in western Massachusetts. Based on rapid polymerase chain reaction testing, 51 of these patients were positive for H1N1, of which 38 had received a seasonal flu vaccine.

H1N1 patients who had received vaccination were significantly older (70.4 years vs. 59.6 years; P = .016) and were more often smokers (76% vs. 38%; P = .017), compared with patients who were unvaccinated.

The finding that the unvaccinated patients were younger and still had poorer outcomes, “emphasizes the need for widespread vaccination,” Dr. Chandak said.

There were several parameters that trended in favor of vaccination, but did not reach statistical significance due to the relatively small sample size, Dr. Chandak said. These included a trend towards more ICU admission in the unvaccinated, compared with vaccinated patients (21% and 12%, respectively; P = .699), a longer ICU stay (1.7 days and 0.2 days; P = .144), more multiorgan dysfunction syndrome (12% and 6%; P = .654), and more acute respiratory distress syndrome (6% and 0%; P = .547). Vasopressors were needed in a similar proportion of patients (12% of both groups).

During the 2009-2010 flu season, H1N1 was the cause of about 61 million cases of influenza in the United States, 274,000 hospitalizations, and 12,470 deaths, Dr. Chandak reported.

Since the 2010-2011 influenza season, the trivalent influenza vaccine has included antigen from the 2009 pandemic H1N1 influenza A virus. This has prevented between 700,000 and 1.5 million cases of H1N1, up to 10,000 hospitalizations, and as many as 500 deaths, according to surveillance data (Emerg Infect Dis. 2013;19[3]:439-48).

The viral subtype made a strong reappearance in the 2015-2016 flu season when it was again the predominant viral subtype of the season, according to the CDC. Most studies have looked at the effectiveness of the vaccine, but have not studied critical care outcomes in vaccinated versus unvaccinated patients, Dr. Chandak noted.

Dr. Chandak reported having no financial disclosures.

 

BOSTON – In a study of patients without a previous diagnosis of obstructive sleep apnea (OSA), 85% of participants in outpatient arrhythmia clinics had undetected OSA.

The study, which also excluded patients who had ever been treated for OSA, was presented by Colin Shapiro, MD, of the Department of Psychiatry, Toronto Western Hospital, University of Toronto, at the annual meeting of the Associated Professional Sleep Societies.

copyright designer491/Thinkstock

On a 2-night home sleep study, 91% of males and 71% of females were found to have an apnea hypopnea index of 5 or more. Looking at the degrees of apnea, 28% of patients were found to have severe OSA (AHI greater than or equal to 30 events/hour of sleep), 33% had moderate OSA, 24% had mild OSA, and 15% did not have OSA.

A binary logistic regression analysis showed that only age and male gender were significant predictors of OSA.

Along with a home sleep study, researchers tested 75 nonselected consecutive patients (mean age of 64 years; 72% male) from three outpatient arrhythmia clinics for symptoms indicative of OSA using the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS), the Non-Restorative Sleep Scale (NRSS), and other questionnaires.

On the ESS, 32% of patients had a score of 8 or greater, indicating higher than normal daytime sleepiness. Almost half (47%) of patients had a high level of fatigue on the FSS, and symptoms of nonrestorative sleep were detected in 15% (NRSS score greater than or equal to 46).

Dr. Shapiro noted that “high scores suggestive of daytime sleepiness, fatigue, or insomnia did not particularly predict the presence of OSA in patients with arrhythmia.” He concluded that, “with a hit rate of 85%, just about every patient with an arrhythmia should have a sleep study.”

Dr. Shapiro informed attendees at the annual meeting of the Professional Sleep Societies that he was presenting in place of his student and the abstract’s first author, Dr. Asmaa M. Abumuamar, MD, who was denied a visa to attend the meeting. Dr. Abumuamar is from the Toronto Western Research Institute, University of Toronto.

Dr. Shapiro reported that Dr. Abumuamar has no conflicts of interest. Dr. Shapiro reported that he is an investor in the company that supplied the home sleep testing apparatus.

 

BOSTON – In a study of patients without a previous diagnosis of obstructive sleep apnea (OSA), 85% of participants in outpatient arrhythmia clinics had undetected OSA.

The study, which also excluded patients who had ever been treated for OSA, was presented by Colin Shapiro, MD, of the Department of Psychiatry, Toronto Western Hospital, University of Toronto, at the annual meeting of the Associated Professional Sleep Societies.

copyright designer491/Thinkstock

On a 2-night home sleep study, 91% of males and 71% of females were found to have an apnea hypopnea index of 5 or more. Looking at the degrees of apnea, 28% of patients were found to have severe OSA (AHI greater than or equal to 30 events/hour of sleep), 33% had moderate OSA, 24% had mild OSA, and 15% did not have OSA.

A binary logistic regression analysis showed that only age and male gender were significant predictors of OSA.

Along with a home sleep study, researchers tested 75 nonselected consecutive patients (mean age of 64 years; 72% male) from three outpatient arrhythmia clinics for symptoms indicative of OSA using the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS), the Non-Restorative Sleep Scale (NRSS), and other questionnaires.

On the ESS, 32% of patients had a score of 8 or greater, indicating higher than normal daytime sleepiness. Almost half (47%) of patients had a high level of fatigue on the FSS, and symptoms of nonrestorative sleep were detected in 15% (NRSS score greater than or equal to 46).

Dr. Shapiro noted that “high scores suggestive of daytime sleepiness, fatigue, or insomnia did not particularly predict the presence of OSA in patients with arrhythmia.” He concluded that, “with a hit rate of 85%, just about every patient with an arrhythmia should have a sleep study.”

Dr. Shapiro informed attendees at the annual meeting of the Professional Sleep Societies that he was presenting in place of his student and the abstract’s first author, Dr. Asmaa M. Abumuamar, MD, who was denied a visa to attend the meeting. Dr. Abumuamar is from the Toronto Western Research Institute, University of Toronto.

Dr. Shapiro reported that Dr. Abumuamar has no conflicts of interest. Dr. Shapiro reported that he is an investor in the company that supplied the home sleep testing apparatus.

 

BOSTON – In a study of patients without a previous diagnosis of obstructive sleep apnea (OSA), 85% of participants in outpatient arrhythmia clinics had undetected OSA.

The study, which also excluded patients who had ever been treated for OSA, was presented by Colin Shapiro, MD, of the Department of Psychiatry, Toronto Western Hospital, University of Toronto, at the annual meeting of the Associated Professional Sleep Societies.

copyright designer491/Thinkstock

On a 2-night home sleep study, 91% of males and 71% of females were found to have an apnea hypopnea index of 5 or more. Looking at the degrees of apnea, 28% of patients were found to have severe OSA (AHI greater than or equal to 30 events/hour of sleep), 33% had moderate OSA, 24% had mild OSA, and 15% did not have OSA.

A binary logistic regression analysis showed that only age and male gender were significant predictors of OSA.

Along with a home sleep study, researchers tested 75 nonselected consecutive patients (mean age of 64 years; 72% male) from three outpatient arrhythmia clinics for symptoms indicative of OSA using the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS), the Non-Restorative Sleep Scale (NRSS), and other questionnaires.

On the ESS, 32% of patients had a score of 8 or greater, indicating higher than normal daytime sleepiness. Almost half (47%) of patients had a high level of fatigue on the FSS, and symptoms of nonrestorative sleep were detected in 15% (NRSS score greater than or equal to 46).

Dr. Shapiro noted that “high scores suggestive of daytime sleepiness, fatigue, or insomnia did not particularly predict the presence of OSA in patients with arrhythmia.” He concluded that, “with a hit rate of 85%, just about every patient with an arrhythmia should have a sleep study.”

Dr. Shapiro informed attendees at the annual meeting of the Professional Sleep Societies that he was presenting in place of his student and the abstract’s first author, Dr. Asmaa M. Abumuamar, MD, who was denied a visa to attend the meeting. Dr. Abumuamar is from the Toronto Western Research Institute, University of Toronto.

Dr. Shapiro reported that Dr. Abumuamar has no conflicts of interest. Dr. Shapiro reported that he is an investor in the company that supplied the home sleep testing apparatus.

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

 

BOSTON – Remote monitoring of continuous positive airway pressure (CPAP) use with feedback messaging to patients improves adherence but only when patients opt to receive continual feedback on their usage, according to a study.

Dennis Hwang, MD, medical director of Kaiser Permanent Fontana Medical Center in California and his colleagues designed the four-arm Tele-OSA study to evaluate the impact of two automated telemedicine interventions: an obstructive sleep apnea (OSA) education program (provided by Emmi Solutions) and a CPAP remote monitoring system with automated patient feedback (U-Sleep, ResMed). Dr. Hwang, who is also cochair of sleep medicine at Southern California Permanente Medical Group, presented his findings at the annual meeting of the Associated Professional Sleep Societies.

Debra L. Beck/Frontline Medical News

A total of 1,455 patients with OSA were randomized to usual care, usual care + tele-education, usual care + telemonitoring, or usual care and both tele-education and telemonitoring. The tele-education provided OSA and CPAP web-based education, offered patients a personalized invitation via email, was interactive, allowed for repeat viewing, and tracked patient viewing status. The telemonitoring system used automated algorithms to process the uploaded CPAP data. If the patient met certain thresholds, such as no CPAP-data for 2 consecutive days or CPAP usage greater than 4 hours for 3 consecutive nights, a message was automatically sent either by text, email, or phone to the patient.

CPAP adherence was compared at 3 months and 1 year for patients in all four groups. Dr. Hwang reported findings from 556 patients who completed one-year follow-up.

At 90 days, patients assigned to either of the telemonitoring arms had significantly higher CPAP usage than those who did not receive telemonitoring.

However, at 3 months when the study protocol called for the automated messaging to be turned off, CPAP adherence dropped off. By 8 months, adherence in patients using the telemonitoring system was no different from that in those who never received the automated messaging. That would have been the end of the story, except that there was a glitch in the system.

“Perhaps serendipitously, we had a group of patients, about one-third, for whom we inadvertently did not turn off the messaging,” explained Dr. Hwang. “In these patients who continued to receive feedback, CPAP usage remained elevated throughout the course of the year and, at 12 months, was significantly higher than in the patients who were not receiving any kind of messaging.”

Dr. Hwang added that the telemonitoring required no additional provider intervention, “suggesting that this could be a cost-effective strategy.”

Only one-third of patients (66.7%) assigned to one of the tele-education groups viewed the video. Additionally, the researchers found that, whether patients used the tele-education alone or in combination with the telemonitoring, tele-education use had no impact on 90-day compliance with CPAP.

Dr. Hwang received support from the American Sleep Medicine Foundation and ResMed Science.

 

BOSTON – Daytime sleepiness in cognitively intact older adults was significantly associated with subsequent neuroimaging evidence of brain amyloid deposition, according to a data analysis presented at the annual meeting of the Associated Professional Sleep Societies.

Self-reported regular nappers were also more likely to have brain amyloid on subsequent imaging, compared with non-nappers, but this difference just missed statistical significance.

Wavebreakmedia Ltd/Thinkstock

Alzheimer’s disease is characterized by extracellular beta-amyloid deposition and intraneuronal neurofibrillary tangles. In 2009, researchers at Washington University in St. Louis showed that sleep restriction promoted beta-amyloid deposition in a mouse model of Alzheimer’s disease. (Kang et al. Science. 2009).

Complementing these findings, Adam P. Spira, PhD, and his colleagues from John’s Hopkins University, Baltimore, previously published a study showing that self-reported sleep duration and poorer sleep quality were associated with greater beta-amyloid deposition in cognitively normal adults. (Spira et al. JAMA Neurology, 2013).

This new study by Dr. Spira and his colleagues sought to look at the link between excessive daytime sleepiness (EDS)/napping in older adults and beta-amyloid burden 15 years later as determined by positron emission tomography (PET) scanning. EDS, defined as a level of sleepiness during the day sufficient to interfere with daily activities, is a common manifestation of sleep disorders, in particular sleep disordered breathing, and is tied to cognitive impairment and accidents.

In unadjusted analyses, participants with EDS were beyond three times more likely to be beta-amyloid+ (odds ratio, 3.37), compared with those who did not meet criteria for EDS. This finding remained significant after adjustment for age, body mass index, and education level (OR, 2.59).

Nappers had an almost twofold greater odds of being beta-amyloid+ than non-nappers after adjustment, but this difference was not statistically meaningful (multivariate adjusted odds ratio, 1.82).

The researchers analyzed data on 124 participants drawn from the National Institute of Aging’s Baltimore Longitudinal Study of Aging (BLSA), the longest-running study of human aging in the U.S. The mean age of these patients at baseline was 60.1 years, and 50.8% of the sample was female. All participants were determined to be cognitively normal at baseline.

At the beginning of the study, participants were asked about their daytime sleepiness and napping habits. Those who reported often being drowsy or falling asleep during the daytime when they preferred to be awake were considered to having EDS. Those who napped once or twice a week or more were considered nappers.

About one-quarter of participants (24.4%) reported EDS, and 28.5% identified themselves as regular nappers. An average of 15.7 years later, participants completed Pittsburgh Compound B PET imaging, at which time 34.7% were deemed beta-amyloid+.

“We were kind of shocked that a single question with a yes/no response was robustly associated with [beta-amyloid] status that many years later,” reported Dr. Spira.

Still unknown, he added, is whether there is utility in quantifying or screening for preclinical Alzheimer’s disease risk using sleep variables. Also unclear is how EDS itself might drive beta-amyloid deposition. “What is likely to be happening here is something like sleep disordered breathing – which has been linked to cognitive impairment and dementia and has been linked to [Alzheimer’s disease] biomarkers – is driving this association,” he speculated.

“We have to keep in mind that even the people at baseline, even though they were cognitively normal, may have had some beta-amyloid deposition, which might have contributed to their EDS,” said Dr. Spira.

Dr. Spira intends to conduct a prospective study using laboratory-based sleep testing (polysomnography) and repeated measures of brain amyloid to clarify whether sleep disordered breathing or other factors were driving the association he found.

Dr. Spira reported having no financial disclosures. This study was supported by grants from the National Institute on Aging.

 

BOSTON – Daytime sleepiness in cognitively intact older adults was significantly associated with subsequent neuroimaging evidence of brain amyloid deposition, according to a data analysis presented at the annual meeting of the Associated Professional Sleep Societies.

Self-reported regular nappers were also more likely to have brain amyloid on subsequent imaging, compared with non-nappers, but this difference just missed statistical significance.

Wavebreakmedia Ltd/Thinkstock

Alzheimer’s disease is characterized by extracellular beta-amyloid deposition and intraneuronal neurofibrillary tangles. In 2009, researchers at Washington University in St. Louis showed that sleep restriction promoted beta-amyloid deposition in a mouse model of Alzheimer’s disease. (Kang et al. Science. 2009).

Complementing these findings, Adam P. Spira, PhD, and his colleagues from John’s Hopkins University, Baltimore, previously published a study showing that self-reported sleep duration and poorer sleep quality were associated with greater beta-amyloid deposition in cognitively normal adults. (Spira et al. JAMA Neurology, 2013).

This new study by Dr. Spira and his colleagues sought to look at the link between excessive daytime sleepiness (EDS)/napping in older adults and beta-amyloid burden 15 years later as determined by positron emission tomography (PET) scanning. EDS, defined as a level of sleepiness during the day sufficient to interfere with daily activities, is a common manifestation of sleep disorders, in particular sleep disordered breathing, and is tied to cognitive impairment and accidents.

In unadjusted analyses, participants with EDS were beyond three times more likely to be beta-amyloid+ (odds ratio, 3.37), compared with those who did not meet criteria for EDS. This finding remained significant after adjustment for age, body mass index, and education level (OR, 2.59).

Nappers had an almost twofold greater odds of being beta-amyloid+ than non-nappers after adjustment, but this difference was not statistically meaningful (multivariate adjusted odds ratio, 1.82).

The researchers analyzed data on 124 participants drawn from the National Institute of Aging’s Baltimore Longitudinal Study of Aging (BLSA), the longest-running study of human aging in the U.S. The mean age of these patients at baseline was 60.1 years, and 50.8% of the sample was female. All participants were determined to be cognitively normal at baseline.

At the beginning of the study, participants were asked about their daytime sleepiness and napping habits. Those who reported often being drowsy or falling asleep during the daytime when they preferred to be awake were considered to having EDS. Those who napped once or twice a week or more were considered nappers.

About one-quarter of participants (24.4%) reported EDS, and 28.5% identified themselves as regular nappers. An average of 15.7 years later, participants completed Pittsburgh Compound B PET imaging, at which time 34.7% were deemed beta-amyloid+.

“We were kind of shocked that a single question with a yes/no response was robustly associated with [beta-amyloid] status that many years later,” reported Dr. Spira.

Still unknown, he added, is whether there is utility in quantifying or screening for preclinical Alzheimer’s disease risk using sleep variables. Also unclear is how EDS itself might drive beta-amyloid deposition. “What is likely to be happening here is something like sleep disordered breathing – which has been linked to cognitive impairment and dementia and has been linked to [Alzheimer’s disease] biomarkers – is driving this association,” he speculated.

“We have to keep in mind that even the people at baseline, even though they were cognitively normal, may have had some beta-amyloid deposition, which might have contributed to their EDS,” said Dr. Spira.

Dr. Spira intends to conduct a prospective study using laboratory-based sleep testing (polysomnography) and repeated measures of brain amyloid to clarify whether sleep disordered breathing or other factors were driving the association he found.

Dr. Spira reported having no financial disclosures. This study was supported by grants from the National Institute on Aging.

 

BOSTON – Daytime sleepiness in cognitively intact older adults was significantly associated with subsequent neuroimaging evidence of brain amyloid deposition, according to a data analysis presented at the annual meeting of the Associated Professional Sleep Societies.

Self-reported regular nappers were also more likely to have brain amyloid on subsequent imaging, compared with non-nappers, but this difference just missed statistical significance.

Wavebreakmedia Ltd/Thinkstock

Alzheimer’s disease is characterized by extracellular beta-amyloid deposition and intraneuronal neurofibrillary tangles. In 2009, researchers at Washington University in St. Louis showed that sleep restriction promoted beta-amyloid deposition in a mouse model of Alzheimer’s disease. (Kang et al. Science. 2009).

Complementing these findings, Adam P. Spira, PhD, and his colleagues from John’s Hopkins University, Baltimore, previously published a study showing that self-reported sleep duration and poorer sleep quality were associated with greater beta-amyloid deposition in cognitively normal adults. (Spira et al. JAMA Neurology, 2013).

This new study by Dr. Spira and his colleagues sought to look at the link between excessive daytime sleepiness (EDS)/napping in older adults and beta-amyloid burden 15 years later as determined by positron emission tomography (PET) scanning. EDS, defined as a level of sleepiness during the day sufficient to interfere with daily activities, is a common manifestation of sleep disorders, in particular sleep disordered breathing, and is tied to cognitive impairment and accidents.

In unadjusted analyses, participants with EDS were beyond three times more likely to be beta-amyloid+ (odds ratio, 3.37), compared with those who did not meet criteria for EDS. This finding remained significant after adjustment for age, body mass index, and education level (OR, 2.59).

Nappers had an almost twofold greater odds of being beta-amyloid+ than non-nappers after adjustment, but this difference was not statistically meaningful (multivariate adjusted odds ratio, 1.82).

The researchers analyzed data on 124 participants drawn from the National Institute of Aging’s Baltimore Longitudinal Study of Aging (BLSA), the longest-running study of human aging in the U.S. The mean age of these patients at baseline was 60.1 years, and 50.8% of the sample was female. All participants were determined to be cognitively normal at baseline.

At the beginning of the study, participants were asked about their daytime sleepiness and napping habits. Those who reported often being drowsy or falling asleep during the daytime when they preferred to be awake were considered to having EDS. Those who napped once or twice a week or more were considered nappers.

About one-quarter of participants (24.4%) reported EDS, and 28.5% identified themselves as regular nappers. An average of 15.7 years later, participants completed Pittsburgh Compound B PET imaging, at which time 34.7% were deemed beta-amyloid+.

“We were kind of shocked that a single question with a yes/no response was robustly associated with [beta-amyloid] status that many years later,” reported Dr. Spira.

Still unknown, he added, is whether there is utility in quantifying or screening for preclinical Alzheimer’s disease risk using sleep variables. Also unclear is how EDS itself might drive beta-amyloid deposition. “What is likely to be happening here is something like sleep disordered breathing – which has been linked to cognitive impairment and dementia and has been linked to [Alzheimer’s disease] biomarkers – is driving this association,” he speculated.

“We have to keep in mind that even the people at baseline, even though they were cognitively normal, may have had some beta-amyloid deposition, which might have contributed to their EDS,” said Dr. Spira.

Dr. Spira intends to conduct a prospective study using laboratory-based sleep testing (polysomnography) and repeated measures of brain amyloid to clarify whether sleep disordered breathing or other factors were driving the association he found.

Dr. Spira reported having no financial disclosures. This study was supported by grants from the National Institute on Aging.

 

BOSTON – Newborns exposed to obstructive sleep apnea (OSA) in utero are at a higher risk of being diagnosed with congenital anomalies, according to a new study presented at the annual meeting of the Associated Professional Sleep Societies.

The researchers’ analysis covered data from more than 1.4 million births during 2010-2014. Circulatory, musculoskeletal, and central nervous systems were among the types of anomalies they saw in the 17.3% of babies born to mothers who had OSA during pregnancy. These babies were also more likely to require intensive care at birth, compared with those born to mothers who had not been diagnosed with OSA.

While more than 17% of babies born to mothers with OSA had congenital anomalies, 10.6% of the newborns of mothers without an OSA diagnosis had the same types of health issues (P less than .001). This difference between the babies in the two groups remained significant after a multivariate analysis that adjusted for potential confounding variables, including maternal obesity or diabetes (odd ratio, 1.26; P less than .05). The highest risk was for musculoskeletal anomalies, with a significant 89% increase in risk seen after the adjustment.

Additionally, the investigators found that the 0.1% of women who had a diagnosis of OSA were 2.76 times more likely to have babies that required some kind of resuscitative effort at birth. Specifically, 0.5% of the newborns of the mothers with OSA required resuscitation, compared with 0.1% of the other group’s babies. The newborns of women with OSA were also 2.25 times more likely to have a longer hospital stay.

Mothers with OSA were older and more likely to be non-Hispanic black and have a diagnosis of obesity, tobacco use, and drug use but not alcohol use.

“We can’t say for sure that sleep apnea is causing these outcomes,” said abstract presenter and principal investigator Ghada Bourjeily, MD, of Brown University and Miriam Hospital, both in Providence, R.I., in an interview.

“We know that women who have sleep apnea also often have other morbidities, so we don’t know what might have contributed to the congenital outcomes,” said Dr. Bourjeily. “We also don’t know if treating sleep apnea can reverse or prevent birth complications or even maternal complications, like preeclampsia or gestational diabetes.”

Ongoing studies are looking at maternal continuous positive airway pressure therapy use and neonatal outcomes, but “they are nothing to write home about yet,” she said.

“This is an underdiagnosed condition and it’s probably undercoded too, but we know from another study that the prevalence of OSA in the first trimester in an all-comers population that was screened for the condition is 4%,” said Dr. Bourjeily. “If another 3% of [the study participants] actually had OSA, then all of these findings are potentially underestimated.”

The majority of OSA in pregnant women that has been identified in prospective studies is mild and not necessarily something that most physicians would treat, she noted. “In our study, the ones who were diagnosed were those who probably went to their doctors and complained of sleepiness or loud snoring.”

The researchers also determined that the newborns of mothers with sleep apnea were more likely to be admitted to an intensive care unit (25.3% vs. 8.1%) or a special care nursery (34.9% vs. 13.6%).

A diagnosis of OSA was established when a diagnosis code for OSA was present on the delivery discharge record. Maternal and infant outcomes were collected for ICD-9 and procedural codes.

Dr. Bourjeily received research equipment support from Respironics.

 

BOSTON – Newborns exposed to obstructive sleep apnea (OSA) in utero are at a higher risk of being diagnosed with congenital anomalies, according to a new study presented at the annual meeting of the Associated Professional Sleep Societies.

The researchers’ analysis covered data from more than 1.4 million births during 2010-2014. Circulatory, musculoskeletal, and central nervous systems were among the types of anomalies they saw in the 17.3% of babies born to mothers who had OSA during pregnancy. These babies were also more likely to require intensive care at birth, compared with those born to mothers who had not been diagnosed with OSA.

While more than 17% of babies born to mothers with OSA had congenital anomalies, 10.6% of the newborns of mothers without an OSA diagnosis had the same types of health issues (P less than .001). This difference between the babies in the two groups remained significant after a multivariate analysis that adjusted for potential confounding variables, including maternal obesity or diabetes (odd ratio, 1.26; P less than .05). The highest risk was for musculoskeletal anomalies, with a significant 89% increase in risk seen after the adjustment.

Additionally, the investigators found that the 0.1% of women who had a diagnosis of OSA were 2.76 times more likely to have babies that required some kind of resuscitative effort at birth. Specifically, 0.5% of the newborns of the mothers with OSA required resuscitation, compared with 0.1% of the other group’s babies. The newborns of women with OSA were also 2.25 times more likely to have a longer hospital stay.

Mothers with OSA were older and more likely to be non-Hispanic black and have a diagnosis of obesity, tobacco use, and drug use but not alcohol use.

“We can’t say for sure that sleep apnea is causing these outcomes,” said abstract presenter and principal investigator Ghada Bourjeily, MD, of Brown University and Miriam Hospital, both in Providence, R.I., in an interview.

“We know that women who have sleep apnea also often have other morbidities, so we don’t know what might have contributed to the congenital outcomes,” said Dr. Bourjeily. “We also don’t know if treating sleep apnea can reverse or prevent birth complications or even maternal complications, like preeclampsia or gestational diabetes.”

Ongoing studies are looking at maternal continuous positive airway pressure therapy use and neonatal outcomes, but “they are nothing to write home about yet,” she said.

“This is an underdiagnosed condition and it’s probably undercoded too, but we know from another study that the prevalence of OSA in the first trimester in an all-comers population that was screened for the condition is 4%,” said Dr. Bourjeily. “If another 3% of [the study participants] actually had OSA, then all of these findings are potentially underestimated.”

The majority of OSA in pregnant women that has been identified in prospective studies is mild and not necessarily something that most physicians would treat, she noted. “In our study, the ones who were diagnosed were those who probably went to their doctors and complained of sleepiness or loud snoring.”

The researchers also determined that the newborns of mothers with sleep apnea were more likely to be admitted to an intensive care unit (25.3% vs. 8.1%) or a special care nursery (34.9% vs. 13.6%).

A diagnosis of OSA was established when a diagnosis code for OSA was present on the delivery discharge record. Maternal and infant outcomes were collected for ICD-9 and procedural codes.

Dr. Bourjeily received research equipment support from Respironics.

 

BOSTON – Newborns exposed to obstructive sleep apnea (OSA) in utero are at a higher risk of being diagnosed with congenital anomalies, according to a new study presented at the annual meeting of the Associated Professional Sleep Societies.

The researchers’ analysis covered data from more than 1.4 million births during 2010-2014. Circulatory, musculoskeletal, and central nervous systems were among the types of anomalies they saw in the 17.3% of babies born to mothers who had OSA during pregnancy. These babies were also more likely to require intensive care at birth, compared with those born to mothers who had not been diagnosed with OSA.

While more than 17% of babies born to mothers with OSA had congenital anomalies, 10.6% of the newborns of mothers without an OSA diagnosis had the same types of health issues (P less than .001). This difference between the babies in the two groups remained significant after a multivariate analysis that adjusted for potential confounding variables, including maternal obesity or diabetes (odd ratio, 1.26; P less than .05). The highest risk was for musculoskeletal anomalies, with a significant 89% increase in risk seen after the adjustment.

Additionally, the investigators found that the 0.1% of women who had a diagnosis of OSA were 2.76 times more likely to have babies that required some kind of resuscitative effort at birth. Specifically, 0.5% of the newborns of the mothers with OSA required resuscitation, compared with 0.1% of the other group’s babies. The newborns of women with OSA were also 2.25 times more likely to have a longer hospital stay.

Mothers with OSA were older and more likely to be non-Hispanic black and have a diagnosis of obesity, tobacco use, and drug use but not alcohol use.

“We can’t say for sure that sleep apnea is causing these outcomes,” said abstract presenter and principal investigator Ghada Bourjeily, MD, of Brown University and Miriam Hospital, both in Providence, R.I., in an interview.

“We know that women who have sleep apnea also often have other morbidities, so we don’t know what might have contributed to the congenital outcomes,” said Dr. Bourjeily. “We also don’t know if treating sleep apnea can reverse or prevent birth complications or even maternal complications, like preeclampsia or gestational diabetes.”

Ongoing studies are looking at maternal continuous positive airway pressure therapy use and neonatal outcomes, but “they are nothing to write home about yet,” she said.

“This is an underdiagnosed condition and it’s probably undercoded too, but we know from another study that the prevalence of OSA in the first trimester in an all-comers population that was screened for the condition is 4%,” said Dr. Bourjeily. “If another 3% of [the study participants] actually had OSA, then all of these findings are potentially underestimated.”

The majority of OSA in pregnant women that has been identified in prospective studies is mild and not necessarily something that most physicians would treat, she noted. “In our study, the ones who were diagnosed were those who probably went to their doctors and complained of sleepiness or loud snoring.”

The researchers also determined that the newborns of mothers with sleep apnea were more likely to be admitted to an intensive care unit (25.3% vs. 8.1%) or a special care nursery (34.9% vs. 13.6%).

A diagnosis of OSA was established when a diagnosis code for OSA was present on the delivery discharge record. Maternal and infant outcomes were collected for ICD-9 and procedural codes.

Dr. Bourjeily received research equipment support from Respironics.