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DDW: Budesonide improves dysphagia, histology, and endoscopic findings in EoE
WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.
Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.
“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”
Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.
The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.
Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.
At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.
From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).
Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.
During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.
After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.
Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.
The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.
“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”
The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.
WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.
Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.
“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”
Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.
The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.
Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.
At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.
From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).
Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.
During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.
After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.
Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.
The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.
“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”
The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.
WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.
Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.
“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”
Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.
The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.
Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.
At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.
From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).
Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.
During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.
After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.
Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.
The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.
“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”
The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.
AT DDW 2015
Key clinical point: A mucoadherent oral formulation of budesonide shows promise as an effective treatment for eosinophilic esophagitis (EoE), with a favorable safety profile.
Major finding: Beneficial effects of oral budesonide in a study of adolescents and adults with EoE included a histologic response rate of 39% and significantly improved dysphagia symptoms.
Data source: A randomized, double-blind multicenter U.S. study evaluated the healing effects and response to of oral budesonide vs. placebo in 93 patients with EoE, aged 11-40 years.
Disclosures: The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Dr. Hirano disclosed having worked as a consultant for Meritage.
Broad spectrum–antibiotic Use Shifted Following National Guideline Publication
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information abut the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information abut the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information abut the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
FROM PEDIATRICS
Broad spectrum–antibiotic use shifted following national guideline publication
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information about the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information about the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
Use of broad-spectrum antibiotics to treat pediatric pneumonia dropped considerably following the publication of national guidelines that recommended narrow-spectrum antibiotics, according to a recent study.
The guidelines released by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) in August 2011 “emphasized the use of a single, narrow-spectrum antibiotic (i.e., penicillin/ampicillin) for vaccinated children hospitalized with uncomplicated community-acquired pneumonia,” based on evidence that Streptococcus pneumoniae most commonly caused the illness and that incidence of penicillin-resistant pneumococcal disease had dropped after the vaccine’s introduction.
“Overall, use of third-generation cephalosporins declined significantly after release of the guidelines, whereas penicillin/ampicillin use increased,” reported Dr. Derek Williams of Monroe Carell Jr. Children’s Hospital and Vanderbilt University in Nashville, Tenn., and his associates. “We noted consistent trends across study sites, although changes were most apparent in institutions that conducted active hospital-based educational efforts to disseminate the PIDS/IDSA guidelines,” they wrote (Pediatrics 2015 June 22 [doi:10.1542/peds.2014-3047]).
The researchers analyzed the records of all 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah. In the year before the new guidelines, all three hospitals most commonly used the broad-spectrum antibiotics, with prescription rates ranging from 43% to 61% for third-generation cephalosporins, compared with rates of 1%-9% for penicillin and ampicillin prescriptions. Overall, 52.8% of children received third-generation cephalosporins to treat their pneumonia and 2.7% received penicillin or ampicillin before the guidelines.
Nine months after the guidelines had been published, the use of third-generation cephalosporins dropped 12.4 percentage points and the use of penicillin and ampicillin increased 11.3 percentage points, Dr. Williams and his associates said.
The largest shift in prescribing patterns occurred at the two hospitals that held pediatric departmental educational conferences within 4 months of the new guidelines. The third hospital, which did not formally distribute information about the guidelines, saw the smallest reduction in broad spectrum–antibiotic use.
Although all three hospitals reported having antimicrobial stewardship programs, none had a community-acquired pneumonia practice guideline during the study period and none of the programs specifically focused on community-acquired pneumonia or restrictions on third-generation cephalosporins, aminopenicillins, or macrolides.
The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: Broad spectrum–antibiotic use for community-acquired pneumonia dropped following 2011 guidelines.
Major finding: Third generation–cephalosporin use dropped 12.4 percentage points and the use of penicillin/ampicillin increased 11.3 percentage points.
Data source: The findings are based on an analysis of antibiotic prescribing trends for 2,121 children hospitalized with community-acquired pneumonia between January 2010 and June 2012 at three hospitals in Tennessee and Utah.
Disclosures: The research was supported by the National Institute of Allergy and Infectious Diseases, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention. The authors reported no relevant financial disclosures.
Sleep matters
Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?
The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.
The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.
So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.
Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.
As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.
Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.
Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.
Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.
Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?
The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.
The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.
So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.
Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.
As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.
Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.
Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.
Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.
Sleep deprivation being a health issue in adolescence is no surprise. We hear repeated reports on cellphone use and excessive video gaming as contributors to sleep deprivation, but how many pediatricians are actually warning their patient during annual exams about the health impact of sleep deprivation?
The American Academy of Pediatrics recently published its policy on sleep and recommended adolescents get at least 8.5 hours of sleep per night and that school start time for middle schools be 8:30 a.m. (Pediatrics 2014;134:642-9). Despite this recommendation, more than 60% of U.S. schools have start times earlier than 8:00 a.m. A recent study also showed that 59% of 6th-8th graders and 87% of high school students obtained less the recommended 8.5 hours.
The reasoning behind the recommendation was based on the natural change in sleep cycle that occurs during adolescence, in which the circadian rhythm changes, resulting in decreased secretion of melatonin and delayed onset of sleep. With later start times, adolescents actually get up to an extra hour of sleep, which in turn results in fewer absences, improved focus, concentration, and better behavior (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
But beyond biologic cause for delayed sleep, social media, texting, and video games further impact the amount of sleep obtained, which leaves the majority of teens sleep deprived. Watching TV more than 3 hours per night impacts your ability not only to fall asleep, but to stay asleep, which again increases daytime sleepiness. Many may think that the “weekend catch-up” might ameliorate the deprivation, but studies show that the inconsistency of appropriate sleep further disrupts the wake-sleep cycles and further reduces the secretion of melatonin.
So how does sleep deprivation impact health? The obvious increased daytime sleepiness which results in poor concentration and focus is well known, and clearly contributes to the number of car accidents in this age group. But there are clear physiologic changes that occur when there is inadequate sleep that result in increased risk for diabetes, obesity, depression, cardiovascular disease, and even Alzheimer’s (Psychiatry Res. 2010;176:34-9; Sleep 2004;27:1351-8; Endocr. Dev. 2010;17:11-21). Lack of sleep has shown alterations in metabolic profiles, such as insulin, cortisol, and leptin, which lead to insulin resistance, increased sympathetic nervous system activity, increased hunger, and decreased satiety (Pediatrics 2014 [doi:10.1542/peds.2014-1697]).
The resulting lack of sleep in adolescence has cause increased intake of caffeine as well. Recent surveys show that caffeine use has skyrocketed this age group. If it is taken in the form of energy drinks, coffee, or soda, people who drink excessive caffeine are twice as likely to have sleep issues and shortened REM sleep (J. Adolesc. 2009;32:1189-207). It suppresses appetite and has withdrawal symptoms that further increase daytime sleepiness.
Adolescents also show increased use of sleep aids and stimulant drinks that have significant side effects of residual daytime sleepiness and tachycardia, respectively. So the treatment is further impacting the problem.
As physicians, we need to emphasize the physiologic impact of sleep deprivation and how it impacts many of the symptoms with which patients present. Many patients may overlook limited sleep as a cause of their symptoms.
Natural alternatives for improved sleep include chamomile, passionflower, or valerian, which come as a tea, capsule, liquid, or essential oil. Magnesium with or without calcium also is commonly used. Although all are deemed generally safe, there is no definitive effective dose in pediatrics, and they are not without side effects, so caution should be used when recommending these. Almond milk is a rich source of calcium, and calcium in the brain gets converted to melatonin.
Suggesting to parents that cellphones, video games, and computers be removed from the bedrooms by 9 p.m. will allow for the required 8.5 hours sleep. Avoiding sleeping until noon on weekends will improve sleep cycles. Avoiding caffeinated drinks and eating at late hours also will improve the quality of sleep and lessen daytime sleepiness. But the best advice to parents is for them to be good role models, and for them to get the appropriate amount of sleep, so that they also can avoid the hazards of sleep deprivation.
Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected]. Scan this QR code or go to pediatricnews.com.
Umeclidinium triple therapy improves lung function in COPD
DENVER – Lung function and health-related quality of life improved for COPD patients who received the long-acting muscarinic agent (LAMA) umeclidinium with fixed-dose inhaled corticosteroid/long-acting beta antagonist (LABA) therapy, based on a post hoc analysis of pooled data from four phase III trials.
Compared with inhaled corticosteroid (ICS)/LABA therapy alone, the triple therapy increased the number of rescue-free days, Dr. Thomas Siler, a pulmonologist with Midwest Chest Consultants, St. Charles, Mo., reported at an international conference of the American Thoracic Society.
The analysis involved 819 patients treated with 62.5 mcg of umeclidinium (Ellipta) – an approved maintenance treatment for COPD – plus ICS/LABA, 821 patients treated with 125 mg umeclidinium plus ICS/LABA, and 818 who received placebo and ICS/LABA. Statistically significant improvements were seen with active triple therapy vs. dual therapy plus placebo in forced expiratory volume in 1 second (FEV1) at day 85 (0.130 L) and at all other time points, as well as in 0-6 h weighted mean FEV1 at day 84 (0.152 L), Dr. Siler said.
With active triple therapy vs. dual therapy plus placebo, overall rescue use was reduced by 0.3 puffs/day and the number of rescue-free days increased by 7.1%. Also, St. George’s Respiratory Questionnaire (SGRQ) score at day 84 decreased by 1.55 vs. placebo, and the proportion of SGRQ responders was 41% vs. 31% for umeclidinium vs. placebo (odds ratio, 1.6).
Moderate/severe COPD exacerbations were experienced by 88 patients: 31 (4%) of the umeclidinium group patients and 57 (7%) of the placebo group patients (hazard ratio, 0.53).
The findings were similar in the patients who received off-label 125-mg dosing of umeclidinium, and the incidence of adverse events and serious adverse events was similar across treatment groups. Dr. Siler noted.
Data on the benefits of LAMAs in triple therapy in patients with moderate to very severe COPD are limited. This pooled analysis of data from four randomized, double-blind, parallel-group 12-week trials of once-daily add-on umeclidinium included COPD patients who entered a 4-week run-in on open-label ICS/LABA (either fluticasone furoate/vilanterol 100/25 mcg or fluticasone propionate/salmeterol 250/50 mcg), and who were then randomized to receive 62.5 or 125 mcg of umeclidinium or placebo.
GlaxoSmithKline funded the study.
DENVER – Lung function and health-related quality of life improved for COPD patients who received the long-acting muscarinic agent (LAMA) umeclidinium with fixed-dose inhaled corticosteroid/long-acting beta antagonist (LABA) therapy, based on a post hoc analysis of pooled data from four phase III trials.
Compared with inhaled corticosteroid (ICS)/LABA therapy alone, the triple therapy increased the number of rescue-free days, Dr. Thomas Siler, a pulmonologist with Midwest Chest Consultants, St. Charles, Mo., reported at an international conference of the American Thoracic Society.
The analysis involved 819 patients treated with 62.5 mcg of umeclidinium (Ellipta) – an approved maintenance treatment for COPD – plus ICS/LABA, 821 patients treated with 125 mg umeclidinium plus ICS/LABA, and 818 who received placebo and ICS/LABA. Statistically significant improvements were seen with active triple therapy vs. dual therapy plus placebo in forced expiratory volume in 1 second (FEV1) at day 85 (0.130 L) and at all other time points, as well as in 0-6 h weighted mean FEV1 at day 84 (0.152 L), Dr. Siler said.
With active triple therapy vs. dual therapy plus placebo, overall rescue use was reduced by 0.3 puffs/day and the number of rescue-free days increased by 7.1%. Also, St. George’s Respiratory Questionnaire (SGRQ) score at day 84 decreased by 1.55 vs. placebo, and the proportion of SGRQ responders was 41% vs. 31% for umeclidinium vs. placebo (odds ratio, 1.6).
Moderate/severe COPD exacerbations were experienced by 88 patients: 31 (4%) of the umeclidinium group patients and 57 (7%) of the placebo group patients (hazard ratio, 0.53).
The findings were similar in the patients who received off-label 125-mg dosing of umeclidinium, and the incidence of adverse events and serious adverse events was similar across treatment groups. Dr. Siler noted.
Data on the benefits of LAMAs in triple therapy in patients with moderate to very severe COPD are limited. This pooled analysis of data from four randomized, double-blind, parallel-group 12-week trials of once-daily add-on umeclidinium included COPD patients who entered a 4-week run-in on open-label ICS/LABA (either fluticasone furoate/vilanterol 100/25 mcg or fluticasone propionate/salmeterol 250/50 mcg), and who were then randomized to receive 62.5 or 125 mcg of umeclidinium or placebo.
GlaxoSmithKline funded the study.
DENVER – Lung function and health-related quality of life improved for COPD patients who received the long-acting muscarinic agent (LAMA) umeclidinium with fixed-dose inhaled corticosteroid/long-acting beta antagonist (LABA) therapy, based on a post hoc analysis of pooled data from four phase III trials.
Compared with inhaled corticosteroid (ICS)/LABA therapy alone, the triple therapy increased the number of rescue-free days, Dr. Thomas Siler, a pulmonologist with Midwest Chest Consultants, St. Charles, Mo., reported at an international conference of the American Thoracic Society.
The analysis involved 819 patients treated with 62.5 mcg of umeclidinium (Ellipta) – an approved maintenance treatment for COPD – plus ICS/LABA, 821 patients treated with 125 mg umeclidinium plus ICS/LABA, and 818 who received placebo and ICS/LABA. Statistically significant improvements were seen with active triple therapy vs. dual therapy plus placebo in forced expiratory volume in 1 second (FEV1) at day 85 (0.130 L) and at all other time points, as well as in 0-6 h weighted mean FEV1 at day 84 (0.152 L), Dr. Siler said.
With active triple therapy vs. dual therapy plus placebo, overall rescue use was reduced by 0.3 puffs/day and the number of rescue-free days increased by 7.1%. Also, St. George’s Respiratory Questionnaire (SGRQ) score at day 84 decreased by 1.55 vs. placebo, and the proportion of SGRQ responders was 41% vs. 31% for umeclidinium vs. placebo (odds ratio, 1.6).
Moderate/severe COPD exacerbations were experienced by 88 patients: 31 (4%) of the umeclidinium group patients and 57 (7%) of the placebo group patients (hazard ratio, 0.53).
The findings were similar in the patients who received off-label 125-mg dosing of umeclidinium, and the incidence of adverse events and serious adverse events was similar across treatment groups. Dr. Siler noted.
Data on the benefits of LAMAs in triple therapy in patients with moderate to very severe COPD are limited. This pooled analysis of data from four randomized, double-blind, parallel-group 12-week trials of once-daily add-on umeclidinium included COPD patients who entered a 4-week run-in on open-label ICS/LABA (either fluticasone furoate/vilanterol 100/25 mcg or fluticasone propionate/salmeterol 250/50 mcg), and who were then randomized to receive 62.5 or 125 mcg of umeclidinium or placebo.
GlaxoSmithKline funded the study.
AT ATS 2015
Key clinical point: Adding umeclidinium to fixed-dose inhaled corticosteroid/long-acting beta antagonist therapy might improve lung function and health-related quality of life in patients with chronic obstructive pulmonary disorder.
Major finding: Statistically significant improvements in FEV1 were seen vs. placebo, at day 85 (0.130 L) and at all other time points.
Data source: A post hoc analysis of data from four phase III trials comprising 2,458 patients.
Disclosures: GlaxoSmithKline funded the study.
ATS: Pulmonary rehab plus CPAP boosts sleep apnea outcomes
DENVER – Pulmonary rehabilitation plus continuous positive airway pressure therapy improved pulmonary function, compared with CPAP alone, in a randomized study of 40 patients with obstructive sleep apnea.
While CPAP remains the main treatment option, it doesn’t address the obesity and inactivity levels that can contribute to comorbidities associated with OSA, Katerina Neumonnova, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society. Patients with OSA often describe respiratory symptoms associated with diminished functional capacity and decreased health-related quality of life. Adjunctive pulmonary rehabilitation might improve pulmonary function, allowing for increased activity levels that can lead to improved outcomes.
Obstructive sleep apnea (OSA) improved with CPAP in all patients in the study. However, percent predicted vital capacity increased from 96.4 to 103.2 in the 20 patients randomized to receive pulmonary rehabilitation and CPAP, and decreased from 99.5 to 94.8 in the 20 patients who received CPAP alone. Percent predicted forced expiratory volume in 1 second (FEV1) improved from 91.5 to 96.1 in the pulmonary rehabilitation plus CPAP group, and decreased from 92.1 to 86.3 in the CPAP-only group.
Those who received pulmonary rehabilitation and CPAP also had significantly greater reductions in body mass index and in neck, waist, and hip circumference, said Dr. Neumonnova of Palacky University, Olomouc, Czech Republic. Percentage of weight as body fat significantly decreased in both groups, but the reduction was greater in those who received pulmonary rehabilitation (from 39.4 to 36.9) than in those who got CPAP alone (from 40.1 to 39.1), she said.
The patients, 20 men and 20 women, mean age 54 years, had similar baseline apnea/hypopnea index (greater than 15), pulmonary function, BMI, percentage of body fat, and neck, waist, and hip circumferences.
The 6-week pulmonary rehabilitation program consisted of twice-weekly 60-minute individualized exercise training sessions, combined with education, breathing retraining, respiratory muscle training, and oropharyngeal exercises. Patients were encouraged to steadily increase their levels of activity, measured by steps per day.
Dr. Neumonnova reported having no disclosures.
DENVER – Pulmonary rehabilitation plus continuous positive airway pressure therapy improved pulmonary function, compared with CPAP alone, in a randomized study of 40 patients with obstructive sleep apnea.
While CPAP remains the main treatment option, it doesn’t address the obesity and inactivity levels that can contribute to comorbidities associated with OSA, Katerina Neumonnova, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society. Patients with OSA often describe respiratory symptoms associated with diminished functional capacity and decreased health-related quality of life. Adjunctive pulmonary rehabilitation might improve pulmonary function, allowing for increased activity levels that can lead to improved outcomes.
Obstructive sleep apnea (OSA) improved with CPAP in all patients in the study. However, percent predicted vital capacity increased from 96.4 to 103.2 in the 20 patients randomized to receive pulmonary rehabilitation and CPAP, and decreased from 99.5 to 94.8 in the 20 patients who received CPAP alone. Percent predicted forced expiratory volume in 1 second (FEV1) improved from 91.5 to 96.1 in the pulmonary rehabilitation plus CPAP group, and decreased from 92.1 to 86.3 in the CPAP-only group.
Those who received pulmonary rehabilitation and CPAP also had significantly greater reductions in body mass index and in neck, waist, and hip circumference, said Dr. Neumonnova of Palacky University, Olomouc, Czech Republic. Percentage of weight as body fat significantly decreased in both groups, but the reduction was greater in those who received pulmonary rehabilitation (from 39.4 to 36.9) than in those who got CPAP alone (from 40.1 to 39.1), she said.
The patients, 20 men and 20 women, mean age 54 years, had similar baseline apnea/hypopnea index (greater than 15), pulmonary function, BMI, percentage of body fat, and neck, waist, and hip circumferences.
The 6-week pulmonary rehabilitation program consisted of twice-weekly 60-minute individualized exercise training sessions, combined with education, breathing retraining, respiratory muscle training, and oropharyngeal exercises. Patients were encouraged to steadily increase their levels of activity, measured by steps per day.
Dr. Neumonnova reported having no disclosures.
DENVER – Pulmonary rehabilitation plus continuous positive airway pressure therapy improved pulmonary function, compared with CPAP alone, in a randomized study of 40 patients with obstructive sleep apnea.
While CPAP remains the main treatment option, it doesn’t address the obesity and inactivity levels that can contribute to comorbidities associated with OSA, Katerina Neumonnova, Ph.D., reported during a press briefing at an international conference of the American Thoracic Society. Patients with OSA often describe respiratory symptoms associated with diminished functional capacity and decreased health-related quality of life. Adjunctive pulmonary rehabilitation might improve pulmonary function, allowing for increased activity levels that can lead to improved outcomes.
Obstructive sleep apnea (OSA) improved with CPAP in all patients in the study. However, percent predicted vital capacity increased from 96.4 to 103.2 in the 20 patients randomized to receive pulmonary rehabilitation and CPAP, and decreased from 99.5 to 94.8 in the 20 patients who received CPAP alone. Percent predicted forced expiratory volume in 1 second (FEV1) improved from 91.5 to 96.1 in the pulmonary rehabilitation plus CPAP group, and decreased from 92.1 to 86.3 in the CPAP-only group.
Those who received pulmonary rehabilitation and CPAP also had significantly greater reductions in body mass index and in neck, waist, and hip circumference, said Dr. Neumonnova of Palacky University, Olomouc, Czech Republic. Percentage of weight as body fat significantly decreased in both groups, but the reduction was greater in those who received pulmonary rehabilitation (from 39.4 to 36.9) than in those who got CPAP alone (from 40.1 to 39.1), she said.
The patients, 20 men and 20 women, mean age 54 years, had similar baseline apnea/hypopnea index (greater than 15), pulmonary function, BMI, percentage of body fat, and neck, waist, and hip circumferences.
The 6-week pulmonary rehabilitation program consisted of twice-weekly 60-minute individualized exercise training sessions, combined with education, breathing retraining, respiratory muscle training, and oropharyngeal exercises. Patients were encouraged to steadily increase their levels of activity, measured by steps per day.
Dr. Neumonnova reported having no disclosures.
AT ATS 2015
Key clinical point: Pulmonary rehabilitation could boost outcomes in patients undergoing CPAP treatment for OSA.
Major finding: Percent predicted vital capacity increased from 96.4 to 103.2 in the pulmonary rehabilitation and CPAP group, and decreased from 99.5 to 94.8 in the CPAP-only group.
Data source: A randomized study of 40 patients.
Disclosures: Dr. Neumonnova reported having no disclosures.
‘Dabbing’ on the rise: Is this marijuana use dangerous?
The use of butane hash oil and the inhalation of concentrated tetrahydrocannabinol created through butane extraction, otherwise known as “dabbing,” seems to be on the rise in the United States, and might carry risks beyond that of traditional marijuana, according to John M. Stogner, Ph.D., and Bryan Lee Miller, Ph.D.
Butane hash oil (BHO) is produced by passing butane through a tube filled with cannabis trimmings. The tetrahydrocannabinol (THC) dissolves in the butane, and the mixture is collected. The butane evaporates off, leaving crystals that can be up to 80% THC. This process, known as blasting, can be done at home. However, butane is a dangerous and flammable substance, and the risks tied to blasting are similar to those of methamphetamine production.
Dabbing itself involves inhaling vaporized THC crystals through a glass water pipe using a hollow titanium rod heated by a blowtorch. Aside from the obvious health risk of using a blowtorch while mentally impaired, dabbing also can involve inhalation of off-gassing solder, rust from oxidized metal, and benzene.
There has been little research into the health effects of dabbing. Some sources suggest that substances that cause lung damage are not smoked and there is no risk of bacterial or fungal infection; others suggest that adverse side effects such as loss of consciousness and falls are more common, and that dabbing carries an increased risk of addiction.
Primary care physicians should inform patients of potential risk, but they “should avoid hyperbolic arguments like those of the media that describe dabbing as ‘the crack of pot,’ and instead urge caution. Patients should be advised that research is lacking, information is still largely anecdotal, and the safest option is to refrain from use when definitive answers are absent,” Dr. Stogner and Dr. Miller noted.
Find the full perspective in Pediatrics (doi:10.1542/peds.2015-0454).
The use of butane hash oil and the inhalation of concentrated tetrahydrocannabinol created through butane extraction, otherwise known as “dabbing,” seems to be on the rise in the United States, and might carry risks beyond that of traditional marijuana, according to John M. Stogner, Ph.D., and Bryan Lee Miller, Ph.D.
Butane hash oil (BHO) is produced by passing butane through a tube filled with cannabis trimmings. The tetrahydrocannabinol (THC) dissolves in the butane, and the mixture is collected. The butane evaporates off, leaving crystals that can be up to 80% THC. This process, known as blasting, can be done at home. However, butane is a dangerous and flammable substance, and the risks tied to blasting are similar to those of methamphetamine production.
Dabbing itself involves inhaling vaporized THC crystals through a glass water pipe using a hollow titanium rod heated by a blowtorch. Aside from the obvious health risk of using a blowtorch while mentally impaired, dabbing also can involve inhalation of off-gassing solder, rust from oxidized metal, and benzene.
There has been little research into the health effects of dabbing. Some sources suggest that substances that cause lung damage are not smoked and there is no risk of bacterial or fungal infection; others suggest that adverse side effects such as loss of consciousness and falls are more common, and that dabbing carries an increased risk of addiction.
Primary care physicians should inform patients of potential risk, but they “should avoid hyperbolic arguments like those of the media that describe dabbing as ‘the crack of pot,’ and instead urge caution. Patients should be advised that research is lacking, information is still largely anecdotal, and the safest option is to refrain from use when definitive answers are absent,” Dr. Stogner and Dr. Miller noted.
Find the full perspective in Pediatrics (doi:10.1542/peds.2015-0454).
The use of butane hash oil and the inhalation of concentrated tetrahydrocannabinol created through butane extraction, otherwise known as “dabbing,” seems to be on the rise in the United States, and might carry risks beyond that of traditional marijuana, according to John M. Stogner, Ph.D., and Bryan Lee Miller, Ph.D.
Butane hash oil (BHO) is produced by passing butane through a tube filled with cannabis trimmings. The tetrahydrocannabinol (THC) dissolves in the butane, and the mixture is collected. The butane evaporates off, leaving crystals that can be up to 80% THC. This process, known as blasting, can be done at home. However, butane is a dangerous and flammable substance, and the risks tied to blasting are similar to those of methamphetamine production.
Dabbing itself involves inhaling vaporized THC crystals through a glass water pipe using a hollow titanium rod heated by a blowtorch. Aside from the obvious health risk of using a blowtorch while mentally impaired, dabbing also can involve inhalation of off-gassing solder, rust from oxidized metal, and benzene.
There has been little research into the health effects of dabbing. Some sources suggest that substances that cause lung damage are not smoked and there is no risk of bacterial or fungal infection; others suggest that adverse side effects such as loss of consciousness and falls are more common, and that dabbing carries an increased risk of addiction.
Primary care physicians should inform patients of potential risk, but they “should avoid hyperbolic arguments like those of the media that describe dabbing as ‘the crack of pot,’ and instead urge caution. Patients should be advised that research is lacking, information is still largely anecdotal, and the safest option is to refrain from use when definitive answers are absent,” Dr. Stogner and Dr. Miller noted.
Find the full perspective in Pediatrics (doi:10.1542/peds.2015-0454).
Inspiratory muscle training boosts lung function in ankylosing spondylitis
ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.
Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.
“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”
The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.
The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”
They also completed an exercise training diary in order to assess their compliance with the recommended program.
The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”
The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.
The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.
Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.
Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”
He had no financial disclosures.
On Twitter @Alz_Gal
ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.
Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.
“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”
The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.
The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”
They also completed an exercise training diary in order to assess their compliance with the recommended program.
The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”
The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.
The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.
Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.
Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”
He had no financial disclosures.
On Twitter @Alz_Gal
ROME – A program of inspiratory muscle training combined with standard muscular rehabilitation exercise significantly improved lung function in patients with ankylosing spondylitis.
Compared to patients who engaged only in the rehabilitation exercise, the combination program resulted in significantly greater gains in both physical and physiologic measures of pulmonary function, Dr. Razvan Dragoi reported at the annual meeting of the European League Against Rheumatism.
“We assessed resting pulmonary function and ran cardiopulmonary exercise tests at the start and end of the study and saw significant improvements across all measures of lung function in the group undergoing inspiratory muscle training,” said Dr. Dragoi of the Victor Babes University of Medicine and Pharmacy, Romania. “When you compare these findings with the conventional exercise group – which saw small, nonsignificant improvements – it’s clear that adding inspiratory training to an exercise program has clear health benefits for patients.”
The study randomized 54 patients with ankylosing spondylitis to two exercise interventions, Dr. Dragoi said in an interview. “Both groups in our study performed a weekly group session for about 40 minutes per session, managed by a physiotherapist. They were then provided with simple, step-by-step written instructions with illustrations in order to practice these exercises at home,” 5 days each week, for 40 minutes at a time.
The program consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the hamstring muscles, erector spine muscle, and shoulder muscles; abdominal and diaphragm breathing exercises, and chest expansion exercises. The patients were required to achieve a level of perceived exertion of “somewhat hard.”
They also completed an exercise training diary in order to assess their compliance with the recommended program.
The investigational group, however, added another level of training. “In addition to the conventional exercise training, patients performed supervised inspiratory muscle training, three times a week, totaling 24 sessions. This used a real-time computer-assisted device (Trainair, Project Electronics Limited, United Kingdom).”
The training load was based on 80% of the patient’s sustained maximum inspiratory pressure. The patients started by performing six loaded inspiration with a 60-second rest period between each inspiration. This sequence of six exercises continued with 45-, 30-, and 15-, 10- and 5-second rest periods up to 36 loaded inspirations. The training session duration was about 30 minutes.
The study assessed a number of physical and physiologic endpoints, including chest expansion, forced vital capacity and expiratory volumes, and measures of oxygen and carbon dioxide exchange.
Only one outcome – chest expansion – improved significantly in the control arm, increasing from 69 cm at baseline to 72 cm by 8 weeks. In the intensified arm, however, every outcome improved significantly, including chest expansion (66 cm-94 cm), forced vital capacity (78.6%-82.7%), forced expiratory volume (71%-74.6%), and peak oxygen uptake (1.7-2 L/min). The measures of oxygen and carbon dioxide exchange also showed significant improvements.
Dr. Dragoi didn’t follow the patients to assess how long the exercise-related improvements lasted, but like all exercise, he said, the program would have to be repeated to maintain them. “We do have a follow-up in mind, and will be conducting that soon, but we do not know how many patients will be available for the follow-up.”
He had no financial disclosures.
On Twitter @Alz_Gal
AT EULAR 2015
Key clinical point: Inspiratory muscle training combined with conventional muscle rehabilitation boosted pulmonary function in patients with ankylosing spondylitis.
Major finding: The combination increased chest expansion by almost 30 cm as well as improving physiologic measures of lung function.
Data source: The trail randomized 54 patients to two exercise regimens.
Disclosures: Dr. Dragoi had no financial disclosures.
ATS: Inhaled corticosteroid regimens being used in mild COPD
DENVER – Inhaled corticosteroid plus long-acting beta2-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.
At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta2-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.
The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.
The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.
Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV1) that was less than 80% of predicted normal, and FEV1/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.
At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.
During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV1 area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV1 area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.
For those with prior ICS use, trough FEV1 was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV1 was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.
The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.
This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.
DENVER – Inhaled corticosteroid plus long-acting beta2-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.
At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta2-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.
The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.
The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.
Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV1) that was less than 80% of predicted normal, and FEV1/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.
At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.
During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV1 area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV1 area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.
For those with prior ICS use, trough FEV1 was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV1 was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.
The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.
This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.
DENVER – Inhaled corticosteroid plus long-acting beta2-agonist therapy is overused in patients with mild COPD, based on a post hoc analysis of two pivotal phase III studies.
At entry in the phase III TONADO studies, nearly 40% of patients who were classified as having GOLD A or B disease were receiving ICS maintenance therapy either alone, in free combination, or as fixed-dose combination therapy, Dr. Henrik Watz of the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany, and his colleagues reported at an international conference of the American Thoracic Society.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that use of inhaled corticosteroids (ICS) and long-acting beta2-agonist (LABA) therapy be restricted to patients with severe or very severe COPD (category C or D disease) with frequent exacerbations.
The post-hoc analysis “confirms previous reports highlighting that treatment regimens containing ICS therapy are being used early in the management of patients with COPD, which may not be appropriate based on current GOLD recommendations. Furthermore, consistent improvements in lung function with tiotropium plus olodaterol versus the monocomponents were demonstrated in GOLD A, B, C, and D, regardless of previous ICS use,” Dr. Watz and his associates concluded.
The replicate TONADO studies (TONADO 1 and 2) were multicenter, randomized, double-blind, active-controlled studies evaluating the once-daily long-acting muscarinic agent (LAMA) tiotropium and the LABA olodaterol. The 5,162 patients were randomized to once-daily treatment with inhaled tiotropium plus olodaterol (Respimat FDC), to tiotropium, or to olodaterol for 52 weeks.
Of the study participants, 2,132 had GOLD A/B disease, and 3,030 had GOLD C/D disease, based on exacerbation history and lung function. All had postbronchodilator forced expiratory volume in 1 second (FEV1) that was less than 80% of predicted normal, and FEV1/forced vital capacity of less than 70%. All were current or exsmokers with a history of more than 10 pack-years.
At study entry, 7.2% of the GOLD A/B patients were treated with ICS without a LABA, and 31.1% were receiving ICS and a LABA. Of the GOLD C/D patients, 8.8% were receiving ICS without a LABA and 45% were receiving ICS with a LABA.
During the study, those who received both tiotropium and olodaterol had significant improvements in lung function, compared with those receiving only tiotropium. Among patients who had previously used ICS and received both drugs, the FEV1 area under the curve at 0-3 hours was 0.310 L for GOLD A/B patients and 0.236 L for GOLD C/D patients. For those with no prior ICS use, the FEV1 area under the curve at 0-3 hours was 0.277 L for GOLD A/B patients and 0.251 L for GOLD C/D patients.
For those with prior ICS use, trough FEV1 was 0.160 L for GOLD A/B patients and 0.122 L for GOLD C/D patients receiving both tiotropium and olodaterol. For those with no prior ICS use, trough FEV1 was 0.142 L for GOLD A/B patients and 0.149 L for GOLD C/D patients.
The TONADO studies included patients with moderate to very severe disease, but were conducted when the GOLD guidelines recommended that ICS plus LABA therapy be restricted to those with severe or very severe COPD and repeated exacerbations – before the guidelines were updated to take into account COPD symptoms. The updated guidelines call for ICS plus LABA maintenance therapy for patients in categories C and D disease with frequent exacerbations.
This study was supported by Boehringer Ingelheim, the maker of Respimat FDC.
AT ATS 2015
Key clinical point: Inhaled corticosteroid plus long-acting beta2-agonist therapy is overused in patients with mild COPD.
Major finding: Before study entry, 7.2% of GOLD A/B patients were receiving ICS and 31.1% were receiving ICS plus LABA; 8.8% of GOLD C/D patients were receiving ICS and and 45% were receiving ICS plus LABA.
Data source: A post hoc analysis of data for 5,162 patients from the phase III TONADO studies.
Disclosures: The study was supported by Boehringer Ingelheim, the maker of Respimat FDC.
ATS: QAW039 lowered sputum eosinophilia in eosinophilic asthma
DENVER – After 12 weeks of treatment, a novel oral prostaglandin D2–receptor antagonist significantly suppressed sputum and submucosal eosinophilia without affecting blood eosinophilia levels in patients with eosinophilic asthma, based on results of a single-center randomized trial.
QAW039 given at 225 mg b.i.d. for 12 weeks improved symptom control and asthma-related quality of life, and had a favorable safety profile, lead study author Dr. Rachid Berair said at an international conference of the American Thoracic Society.
QAW039 is under clinical development by Novartis Pharmaceuticals, the sponsor of the trial.
For the study 61 asthmatics with a sputum eosinophil count of 2% or greater were randomized to either QAW039 (30 patients) or placebo (31 patients) for 12 weeks after a 2-week placebo run-in. The study’s primary endpoint was the reduction of sputum eosinophils, while secondary objectives were improvement of asthma control and safety and tolerability. Other endpoints were improvement on the Asthma-related Quality of Life Questionnaire (AQLQ), FEV1, and histologic features of eosinophilic inflammation and airway remodeling, Dr. Berair of the University of Leicester, England, reported.
Mean patient age was 50 years; 90% of patients had asthma at Global Initiative for Asthma (GINA) level IV or greater, while 10% had asthma at GINA V and required up to 10 mg prednisolone daily.
In the trial, patients in the treatment group experienced a 3.5-fold reduction in sputum eosinophils, compared with those in the placebo group (P = .001); as well as a 2.3-fold reduction in submucosal eosinophils, compared with those in the placebo group (P = .041). The numbers of bronchial epithelial eosinophils did not differ between the two groups and there were no significant reductions in blood eosinophil levels between the groups.
Prebronchodilator FEV1 improved in the treatment group compared with the placebo group, but the differences did not reach statistical significance. However postbronchodilator FEV1 improved significantly in the treatment group, compared with the placebo group (P = .020).
The overall AQLQ scores improved significantly in the treatment group, compared with the placebo group (a mean of .59 points; P = .008), as did the AQLQ subdomains of symptoms, activities, emotions, and environmental exposure.
Adverse events were mild and moderate and balanced between both groups. The most common adverse events were respiratory tract infections and asthma exacerbations.
The clinical benefits of QAW039 on the AQLQ, postbronchodilator FEV1, and ACQ7 were no longer evident at 6 weeks after patients stopped taking the drug. “Given the effect of this drug on eosinophils, we can postulate that it would have an effect on asthma exacerbation rates,” Dr. Berair said. “However, our study was not designed nor was of the required duration to show that effect. We need longer studies to look at the effect of this drug on asthma exacerbations.”
The study was sponsored by Novartis. Dr. Berair reported having no relevant financial conflicts.
On Twitter @dougbrunk
DENVER – After 12 weeks of treatment, a novel oral prostaglandin D2–receptor antagonist significantly suppressed sputum and submucosal eosinophilia without affecting blood eosinophilia levels in patients with eosinophilic asthma, based on results of a single-center randomized trial.
QAW039 given at 225 mg b.i.d. for 12 weeks improved symptom control and asthma-related quality of life, and had a favorable safety profile, lead study author Dr. Rachid Berair said at an international conference of the American Thoracic Society.
QAW039 is under clinical development by Novartis Pharmaceuticals, the sponsor of the trial.
For the study 61 asthmatics with a sputum eosinophil count of 2% or greater were randomized to either QAW039 (30 patients) or placebo (31 patients) for 12 weeks after a 2-week placebo run-in. The study’s primary endpoint was the reduction of sputum eosinophils, while secondary objectives were improvement of asthma control and safety and tolerability. Other endpoints were improvement on the Asthma-related Quality of Life Questionnaire (AQLQ), FEV1, and histologic features of eosinophilic inflammation and airway remodeling, Dr. Berair of the University of Leicester, England, reported.
Mean patient age was 50 years; 90% of patients had asthma at Global Initiative for Asthma (GINA) level IV or greater, while 10% had asthma at GINA V and required up to 10 mg prednisolone daily.
In the trial, patients in the treatment group experienced a 3.5-fold reduction in sputum eosinophils, compared with those in the placebo group (P = .001); as well as a 2.3-fold reduction in submucosal eosinophils, compared with those in the placebo group (P = .041). The numbers of bronchial epithelial eosinophils did not differ between the two groups and there were no significant reductions in blood eosinophil levels between the groups.
Prebronchodilator FEV1 improved in the treatment group compared with the placebo group, but the differences did not reach statistical significance. However postbronchodilator FEV1 improved significantly in the treatment group, compared with the placebo group (P = .020).
The overall AQLQ scores improved significantly in the treatment group, compared with the placebo group (a mean of .59 points; P = .008), as did the AQLQ subdomains of symptoms, activities, emotions, and environmental exposure.
Adverse events were mild and moderate and balanced between both groups. The most common adverse events were respiratory tract infections and asthma exacerbations.
The clinical benefits of QAW039 on the AQLQ, postbronchodilator FEV1, and ACQ7 were no longer evident at 6 weeks after patients stopped taking the drug. “Given the effect of this drug on eosinophils, we can postulate that it would have an effect on asthma exacerbation rates,” Dr. Berair said. “However, our study was not designed nor was of the required duration to show that effect. We need longer studies to look at the effect of this drug on asthma exacerbations.”
The study was sponsored by Novartis. Dr. Berair reported having no relevant financial conflicts.
On Twitter @dougbrunk
DENVER – After 12 weeks of treatment, a novel oral prostaglandin D2–receptor antagonist significantly suppressed sputum and submucosal eosinophilia without affecting blood eosinophilia levels in patients with eosinophilic asthma, based on results of a single-center randomized trial.
QAW039 given at 225 mg b.i.d. for 12 weeks improved symptom control and asthma-related quality of life, and had a favorable safety profile, lead study author Dr. Rachid Berair said at an international conference of the American Thoracic Society.
QAW039 is under clinical development by Novartis Pharmaceuticals, the sponsor of the trial.
For the study 61 asthmatics with a sputum eosinophil count of 2% or greater were randomized to either QAW039 (30 patients) or placebo (31 patients) for 12 weeks after a 2-week placebo run-in. The study’s primary endpoint was the reduction of sputum eosinophils, while secondary objectives were improvement of asthma control and safety and tolerability. Other endpoints were improvement on the Asthma-related Quality of Life Questionnaire (AQLQ), FEV1, and histologic features of eosinophilic inflammation and airway remodeling, Dr. Berair of the University of Leicester, England, reported.
Mean patient age was 50 years; 90% of patients had asthma at Global Initiative for Asthma (GINA) level IV or greater, while 10% had asthma at GINA V and required up to 10 mg prednisolone daily.
In the trial, patients in the treatment group experienced a 3.5-fold reduction in sputum eosinophils, compared with those in the placebo group (P = .001); as well as a 2.3-fold reduction in submucosal eosinophils, compared with those in the placebo group (P = .041). The numbers of bronchial epithelial eosinophils did not differ between the two groups and there were no significant reductions in blood eosinophil levels between the groups.
Prebronchodilator FEV1 improved in the treatment group compared with the placebo group, but the differences did not reach statistical significance. However postbronchodilator FEV1 improved significantly in the treatment group, compared with the placebo group (P = .020).
The overall AQLQ scores improved significantly in the treatment group, compared with the placebo group (a mean of .59 points; P = .008), as did the AQLQ subdomains of symptoms, activities, emotions, and environmental exposure.
Adverse events were mild and moderate and balanced between both groups. The most common adverse events were respiratory tract infections and asthma exacerbations.
The clinical benefits of QAW039 on the AQLQ, postbronchodilator FEV1, and ACQ7 were no longer evident at 6 weeks after patients stopped taking the drug. “Given the effect of this drug on eosinophils, we can postulate that it would have an effect on asthma exacerbation rates,” Dr. Berair said. “However, our study was not designed nor was of the required duration to show that effect. We need longer studies to look at the effect of this drug on asthma exacerbations.”
The study was sponsored by Novartis. Dr. Berair reported having no relevant financial conflicts.
On Twitter @dougbrunk
AT ATS 2015
Key clinical point: QAW039 appears to reduce treatment-resistant eosinophilic inflammation in severe asthma.
Major finding: Patients in the QAW039 treatment group experienced a 3.5-fold reduction in sputum eosinophils, compared with those in the placebo group (P = .001), as well as a 2.3-fold reduction in submucosal eosinophils, compared with those in the placebo group (P = .041).
Data source: A randomized trial of 61 patients with eosinophilic asthma who received QAW039 225 b.i.d. or placebo for 12 weeks after a 2-week placebo run-in.
Disclosures: The study was sponsored by Novartis. Dr. Berair reported having no relevant financial conflicts.
