Pulmonary Health Hub

Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.

All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.

Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).

Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.

Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).

“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”

ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.

To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m²; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).

It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.

“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.

The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.

The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.

[email protected]

Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.

All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.

Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).

Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.

Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).

“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”

ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.

To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m²; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).

It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.

“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.

The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.

The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.

[email protected]

Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.

All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.

Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).

Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.

Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).

“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”

ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.

To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m²; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).

It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.

“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.

The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.

The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.

[email protected]

Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin

[email protected]

Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin

[email protected]

Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin

[email protected]

Reslizumab was most effective in patients with high baseline eosinophil counts, two randomized, placebo-controlled studies have determined. The companion studies were simultaneously published in the October issue of Chest.

The drug reslizumab, an anti–interleukin-5 monoclonal antibody, is made by Teva Branded Pharmaceutical Products R&D, who sponsored both studies.

The larger study, comprising 492 patients, found no significant benefit of reslizumab over placebo, Jonathan Corren, MD, and his colleagues wrote (Chest. 2016;150:799-810). But this study didn’t stratify patients by baseline eosinophil levels; a post-hoc subanalysis found a significant benefit in forced expiratory volume in 69 of the patients who had at least 400 eosinophils/microliter (mcL) when treatment began.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

*CORRECTION 12/9/16: An earlier version of this article misstated the infusion frequency.

[email protected]

On Twitter @Alz_Gal

Reslizumab was most effective in patients with high baseline eosinophil counts, two randomized, placebo-controlled studies have determined. The companion studies were simultaneously published in the October issue of Chest.

The drug reslizumab, an anti–interleukin-5 monoclonal antibody, is made by Teva Branded Pharmaceutical Products R&D, who sponsored both studies.

The larger study, comprising 492 patients, found no significant benefit of reslizumab over placebo, Jonathan Corren, MD, and his colleagues wrote (Chest. 2016;150:799-810). But this study didn’t stratify patients by baseline eosinophil levels; a post-hoc subanalysis found a significant benefit in forced expiratory volume in 69 of the patients who had at least 400 eosinophils/microliter (mcL) when treatment began.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

*CORRECTION 12/9/16: An earlier version of this article misstated the infusion frequency.

[email protected]

On Twitter @Alz_Gal

Reslizumab was most effective in patients with high baseline eosinophil counts, two randomized, placebo-controlled studies have determined. The companion studies were simultaneously published in the October issue of Chest.

The drug reslizumab, an anti–interleukin-5 monoclonal antibody, is made by Teva Branded Pharmaceutical Products R&D, who sponsored both studies.

The larger study, comprising 492 patients, found no significant benefit of reslizumab over placebo, Jonathan Corren, MD, and his colleagues wrote (Chest. 2016;150:799-810). But this study didn’t stratify patients by baseline eosinophil levels; a post-hoc subanalysis found a significant benefit in forced expiratory volume in 69 of the patients who had at least 400 eosinophils/microliter (mcL) when treatment began.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

*CORRECTION 12/9/16: An earlier version of this article misstated the infusion frequency.

[email protected]

On Twitter @Alz_Gal

Procalcitonin can help predict which patients with community-acquired pneumonia may require intubation for respiratory failure during a hospital admission.

Compared to those with undetectable levels, patients with a procalcitonin of 5 ng/mL were three times more likely to require invasive respiratory support, and those with a 10 ng/mL level were five times more likely, reported Wesley Self, MD, and his colleagues (Chest. 2016;150[4]:819-28. doi: 10.1016/j.chest.2016.04.010).

While predictive accuracy isn’t good enough to merit use of procalcitonin as a stand-alone test, adding it to existing clinical management tools “is likely to improve identification of patients needing intensive care,” wrote Dr. Self of Vanderbilt University, Nashville, and his colleagues. “An elevated procalcitonin level may help identify these patients without overt clinical signs of impending respiratory failure or shock but who would benefit from early [intensive care unit] admission.”

The team examined serum procalcitonin as a biomarker in a subgroup of patients included in the Etiology of Pneumonia in the Community (EPIC) study of adults hospitalized with community-acquire pneumonia. The primary outcome was the need for invasive respiratory and/or vasopressor support (IRVS) within 72 hours.

Secondarily, they looked at whether adding procalcitonin boosted the performance of accepted pneumonia risk scores, including the American Thoracic Society minor criteria (ATS).

The cohort comprised 1,770 patients with a median age of 57 years. Of these, 115 (6.5%) needed IRVS within 72 hours of admission. Almost 16% were admitted directly into an intensive care unit; almost 7% experienced a delayed transfer from a medical unit into an ICU. The in-hospital mortality was about 2%.

Most (1,642) had an ATS score of less than 3; among these, about 5% needed IRVS. The remainder had a score of 3 or higher; about 30% required IRVS. All had procalcitonin levels pulled at admission. The levels were significantly higher among patients who required IRVS than those who didn’t (1.43 ng/mL vs. 0.14 ng/mL).

A multivariate analysis found that procalcitonin was strongly associated with the risk of IRVS. In patients with undetectable levels, the risk was 4%. At 5-10 ng/mL, the overall risk of IRVS was about 14%. Every 1-ng/mL increase in this range boosted the risk of IRVS by 1%-2%.

Adding the measurement of procalcitonin to traditional pneumonia severity risk scores significantly improved the patients’ performance. When stratified by ATS minor criteria, the risk of IRVS was 4.7% among low-risk patients. That decreased to 2.4% with the addition of undetectable procalcitonin, and increased to 12% with the addition of a 10 ng/mL level.

Conversely, without considering procalcitonin, ATS high-risk patients had almost a 30% risk of IRVS. Among these high-risk patients, IRVS risk dropped to 13% with undetectable procalcitonin and increased to 36% with high procalcitonin.

Adding the biomarker level to the ATS system improved its ability to correctly classify patients, the team said. “Using at least 3 ATS minor criteria alone to indicate high risk, 77 (4.4%) of the 1,770 total patients were misclassified as low-risk and experienced IRVS. Including procalcitonin of at least 0.83 ng/ml in addition … as a high-risk indicator reduced the number of patients with IRVS misclassified as low risk to 44 (2.5%). Adding procalcitonin of at least 0.83 ng/mL as a high-risk indicator resulted in 370 additional patients being classified as high risk, with 33 correctly classified as having IRVS.”

Dr. Self reported financial relationships with multiple pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

Procalcitonin can help predict which patients with community-acquired pneumonia may require intubation for respiratory failure during a hospital admission.

Compared to those with undetectable levels, patients with a procalcitonin of 5 ng/mL were three times more likely to require invasive respiratory support, and those with a 10 ng/mL level were five times more likely, reported Wesley Self, MD, and his colleagues (Chest. 2016;150[4]:819-28. doi: 10.1016/j.chest.2016.04.010).

While predictive accuracy isn’t good enough to merit use of procalcitonin as a stand-alone test, adding it to existing clinical management tools “is likely to improve identification of patients needing intensive care,” wrote Dr. Self of Vanderbilt University, Nashville, and his colleagues. “An elevated procalcitonin level may help identify these patients without overt clinical signs of impending respiratory failure or shock but who would benefit from early [intensive care unit] admission.”

The team examined serum procalcitonin as a biomarker in a subgroup of patients included in the Etiology of Pneumonia in the Community (EPIC) study of adults hospitalized with community-acquire pneumonia. The primary outcome was the need for invasive respiratory and/or vasopressor support (IRVS) within 72 hours.

Secondarily, they looked at whether adding procalcitonin boosted the performance of accepted pneumonia risk scores, including the American Thoracic Society minor criteria (ATS).

The cohort comprised 1,770 patients with a median age of 57 years. Of these, 115 (6.5%) needed IRVS within 72 hours of admission. Almost 16% were admitted directly into an intensive care unit; almost 7% experienced a delayed transfer from a medical unit into an ICU. The in-hospital mortality was about 2%.

Most (1,642) had an ATS score of less than 3; among these, about 5% needed IRVS. The remainder had a score of 3 or higher; about 30% required IRVS. All had procalcitonin levels pulled at admission. The levels were significantly higher among patients who required IRVS than those who didn’t (1.43 ng/mL vs. 0.14 ng/mL).

A multivariate analysis found that procalcitonin was strongly associated with the risk of IRVS. In patients with undetectable levels, the risk was 4%. At 5-10 ng/mL, the overall risk of IRVS was about 14%. Every 1-ng/mL increase in this range boosted the risk of IRVS by 1%-2%.

Adding the measurement of procalcitonin to traditional pneumonia severity risk scores significantly improved the patients’ performance. When stratified by ATS minor criteria, the risk of IRVS was 4.7% among low-risk patients. That decreased to 2.4% with the addition of undetectable procalcitonin, and increased to 12% with the addition of a 10 ng/mL level.

Conversely, without considering procalcitonin, ATS high-risk patients had almost a 30% risk of IRVS. Among these high-risk patients, IRVS risk dropped to 13% with undetectable procalcitonin and increased to 36% with high procalcitonin.

Adding the biomarker level to the ATS system improved its ability to correctly classify patients, the team said. “Using at least 3 ATS minor criteria alone to indicate high risk, 77 (4.4%) of the 1,770 total patients were misclassified as low-risk and experienced IRVS. Including procalcitonin of at least 0.83 ng/ml in addition … as a high-risk indicator reduced the number of patients with IRVS misclassified as low risk to 44 (2.5%). Adding procalcitonin of at least 0.83 ng/mL as a high-risk indicator resulted in 370 additional patients being classified as high risk, with 33 correctly classified as having IRVS.”

Dr. Self reported financial relationships with multiple pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

Procalcitonin can help predict which patients with community-acquired pneumonia may require intubation for respiratory failure during a hospital admission.

Compared to those with undetectable levels, patients with a procalcitonin of 5 ng/mL were three times more likely to require invasive respiratory support, and those with a 10 ng/mL level were five times more likely, reported Wesley Self, MD, and his colleagues (Chest. 2016;150[4]:819-28. doi: 10.1016/j.chest.2016.04.010).

While predictive accuracy isn’t good enough to merit use of procalcitonin as a stand-alone test, adding it to existing clinical management tools “is likely to improve identification of patients needing intensive care,” wrote Dr. Self of Vanderbilt University, Nashville, and his colleagues. “An elevated procalcitonin level may help identify these patients without overt clinical signs of impending respiratory failure or shock but who would benefit from early [intensive care unit] admission.”

The team examined serum procalcitonin as a biomarker in a subgroup of patients included in the Etiology of Pneumonia in the Community (EPIC) study of adults hospitalized with community-acquire pneumonia. The primary outcome was the need for invasive respiratory and/or vasopressor support (IRVS) within 72 hours.

Secondarily, they looked at whether adding procalcitonin boosted the performance of accepted pneumonia risk scores, including the American Thoracic Society minor criteria (ATS).

The cohort comprised 1,770 patients with a median age of 57 years. Of these, 115 (6.5%) needed IRVS within 72 hours of admission. Almost 16% were admitted directly into an intensive care unit; almost 7% experienced a delayed transfer from a medical unit into an ICU. The in-hospital mortality was about 2%.

Most (1,642) had an ATS score of less than 3; among these, about 5% needed IRVS. The remainder had a score of 3 or higher; about 30% required IRVS. All had procalcitonin levels pulled at admission. The levels were significantly higher among patients who required IRVS than those who didn’t (1.43 ng/mL vs. 0.14 ng/mL).

A multivariate analysis found that procalcitonin was strongly associated with the risk of IRVS. In patients with undetectable levels, the risk was 4%. At 5-10 ng/mL, the overall risk of IRVS was about 14%. Every 1-ng/mL increase in this range boosted the risk of IRVS by 1%-2%.

Adding the measurement of procalcitonin to traditional pneumonia severity risk scores significantly improved the patients’ performance. When stratified by ATS minor criteria, the risk of IRVS was 4.7% among low-risk patients. That decreased to 2.4% with the addition of undetectable procalcitonin, and increased to 12% with the addition of a 10 ng/mL level.

Conversely, without considering procalcitonin, ATS high-risk patients had almost a 30% risk of IRVS. Among these high-risk patients, IRVS risk dropped to 13% with undetectable procalcitonin and increased to 36% with high procalcitonin.

Adding the biomarker level to the ATS system improved its ability to correctly classify patients, the team said. “Using at least 3 ATS minor criteria alone to indicate high risk, 77 (4.4%) of the 1,770 total patients were misclassified as low-risk and experienced IRVS. Including procalcitonin of at least 0.83 ng/ml in addition … as a high-risk indicator reduced the number of patients with IRVS misclassified as low risk to 44 (2.5%). Adding procalcitonin of at least 0.83 ng/mL as a high-risk indicator resulted in 370 additional patients being classified as high risk, with 33 correctly classified as having IRVS.”

Dr. Self reported financial relationships with multiple pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

Chronic obstructive pulmonary disease (COPD) patients with depression are less likely to take their maintenance medications, according to a review of Medicare claims by the University of Maryland, Baltimore.

“Clinicians who treat older adults newly diagnosed with COPD should be aware of the development of depression, especially during the first 6 months. As such, clinicians should consider the need to monitor their patients with COPD for … depression [treatment], as well as use of and adherence to prescribed COPD medications. Close management of these and other aspects of newly diagnosed older adults with COPD will help to ensure optimal clinical outcomes,” said the investigators, led by Jennifer Albrecht, PhD, of the department of epidemiology and public health at the University of Maryland.

©designer491/Thinkstock

[email protected]

Chronic obstructive pulmonary disease (COPD) patients with depression are less likely to take their maintenance medications, according to a review of Medicare claims by the University of Maryland, Baltimore.

“Clinicians who treat older adults newly diagnosed with COPD should be aware of the development of depression, especially during the first 6 months. As such, clinicians should consider the need to monitor their patients with COPD for … depression [treatment], as well as use of and adherence to prescribed COPD medications. Close management of these and other aspects of newly diagnosed older adults with COPD will help to ensure optimal clinical outcomes,” said the investigators, led by Jennifer Albrecht, PhD, of the department of epidemiology and public health at the University of Maryland.

©designer491/Thinkstock

[email protected]

Chronic obstructive pulmonary disease (COPD) patients with depression are less likely to take their maintenance medications, according to a review of Medicare claims by the University of Maryland, Baltimore.

“Clinicians who treat older adults newly diagnosed with COPD should be aware of the development of depression, especially during the first 6 months. As such, clinicians should consider the need to monitor their patients with COPD for … depression [treatment], as well as use of and adherence to prescribed COPD medications. Close management of these and other aspects of newly diagnosed older adults with COPD will help to ensure optimal clinical outcomes,” said the investigators, led by Jennifer Albrecht, PhD, of the department of epidemiology and public health at the University of Maryland.

©designer491/Thinkstock

[email protected]

A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.

The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.

Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).

“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).

Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”

In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO₂ between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO₂] between 94% and 98%) or conventional oxygen therapy (allowance of PaO₂ values up to 150 mm Hg or SpO₂ values between 97% and 100%) on an open-label basis.

The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.

Results of modified intent-to-treat analyses showed that daily time-weighted PaO₂ averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO₂, 102 vs. 87 mm Hg; P less than .001).

The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).

The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).

Lengths of ICU stay and hospital stay did not differ between the two groups.

One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.

A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.

The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.

Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).

“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).

Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”

In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO₂ between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO₂] between 94% and 98%) or conventional oxygen therapy (allowance of PaO₂ values up to 150 mm Hg or SpO₂ values between 97% and 100%) on an open-label basis.

The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.

Results of modified intent-to-treat analyses showed that daily time-weighted PaO₂ averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO₂, 102 vs. 87 mm Hg; P less than .001).

The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).

The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).

Lengths of ICU stay and hospital stay did not differ between the two groups.

One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.

A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.

The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.

Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).

“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).

Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”

In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO₂ between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO₂] between 94% and 98%) or conventional oxygen therapy (allowance of PaO₂ values up to 150 mm Hg or SpO₂ values between 97% and 100%) on an open-label basis.

The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.

Results of modified intent-to-treat analyses showed that daily time-weighted PaO₂ averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO₂, 102 vs. 87 mm Hg; P less than .001).

The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).

The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).

Lengths of ICU stay and hospital stay did not differ between the two groups.

One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.

LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.

The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.

Ted Bosworth/Frontline Medical News

LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.

The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.

Ted Bosworth/Frontline Medical News

LONDON – Two large phase III trials with lebrikizumab, a monoclonal antibody that blocks the activity of interleukin-13 (IL-13), produced inconsistent evidence of benefit in patients with uncontrolled asthma, according to a presentation of both sets of data at the annual congress of the European Respiratory Society.

The two phase III studies compared lebrikizumab in doses of 37.5 mg and 125 mg to placebo, each administered subcutaneously every 4 weeks. The results were mixed not only for the primary endpoint, which was a reduction in the rate of exacerbations, but also for several secondary outcomes.

Ted Bosworth/Frontline Medical News

LONDON – Recent evidence of ever smokers having measurable deficits in activity even when lung function is preserved has been further expanded by findings suggesting a different phenotype for patients in this group with radiologic evidence of emphysema, according to data from SPIROMICS (Subpopulations and Intermediate Outcome Measures In COPD Study).

The most recent data were presented at the annual congress of the European Respiratory Society.

Earlier this year, published data drawn from SPIROMICS demonstrated that current and former smokers with preserved lung function (forced expiratory volume in 1 second:forced vital capacity greater than or equal to 0.70) had activity limitations, respiratory symptoms, and exacerbations even though they did not meet the current definition of chronic obstructive pulmonary disease (COPD) (N Engl J Med. 2016;374:1811-21). In the new analysis, further distinctions could be made for patients in this subgroup who also had emphysema on computed tomography (CT).

“Among smokers with preserved lung function, emphysema on CT was associated with reduced activity levels and desaturation on the 6-minute walk test (6MWT),” reported Christian M. Lo Cascio, MD, Columbia University, New York. Compared with smokers with preserved lung function without CT evidence of emphysema, the patients with emphysema on CT did not have more symptoms or exacerbations.

“These and prior findings suggest two distinct but overlapping phenotypes in ever smokers with preserved lung function: an airway disease with respiratory symptoms and frequent exacerbations and emphysema characterized by activity limitation and increased mortality,” said Dr. Lo Cascio.

SPIROMICS, an observational study supported by the National Heart, Lung, and Blood Institute, has enrolled current and former smokers at six centers in the United States to prospectively analyze biomarker, genetic, and clinical data. In the previously published analysis, the focus was on the difference between 849 ever smokers with preserved lung function and 963 patients with mild to moderate COPD. In the data presented by Dr. Lo Cascio, 901 SPIROMICS patients with preserved lung function were analyzed with the focus on the difference between the 66 (7%) who had radiologic evidence of emphysema and the 835 (93%) who had undergone CT indicating that they did not have emphysema.

“Our hypothesis was that the subgroup of patients with emphysema on CT would have lower activity levels, greater desaturation of at least 4% on the 6MWT, more respiratory symptoms, and more exacerbations,” Dr. Lo Cascio reported.

The hypothesis was only half correct. As measured on the activity component of the St. Georges Respiratory Questionnaire, there was about a 10-point (P less than .001) greater reduction in reported activity levels among those with emphysema on CT relative to those without. In addition, the odds ratio (OR) for significant oxygen desaturation, defined as a 4% fall in oxygen saturation of hemoglobin during the 6MWD, was approximately two times greater (P less than .001) for the patients with CT evidence of emphysema.

There were no significant differences between the two groups in walking distance on the 6MWD. Both sets of patients had the same rate of exacerbations and scores on the symptom component of the St. Georges Respiratory Questionnaire, which captures cough, phlegm, wheezing, shortness of breath, and symptom-free days.

Overall, when ever smokers with preserved lung function were subdivided into those with and without CT evidence of emphysema, several similarities were found between the two groups. For those with CT evidence of emphysema and those with no CT evidence of emphysema, mean pack-years of smoking were 43 years and 40 years, respectively, and average body mass indexes were 28.1 and 29.1, respectively. The percentage of patients who had a COPD Assessment Test score of greater than or equal to 10 was 61% among those with CT evidence of emphysema, vs. 50% among those patients without CT evidence of emphysema.

When asked if looking for emphysema on CT in ever smokers with preserved lung function might have clinical utility, Dr. Lo Cascio suggested that it is not yet clear how this information might change management. These data strengthen other evidence from SPIROMICS that ever smokers who do not meet the definition of COPD already have a significant disease burden, he said.

Dr. Lo Cascio reports no relevant financial relationships.

LONDON – Recent evidence of ever smokers having measurable deficits in activity even when lung function is preserved has been further expanded by findings suggesting a different phenotype for patients in this group with radiologic evidence of emphysema, according to data from SPIROMICS (Subpopulations and Intermediate Outcome Measures In COPD Study).

The most recent data were presented at the annual congress of the European Respiratory Society.

Earlier this year, published data drawn from SPIROMICS demonstrated that current and former smokers with preserved lung function (forced expiratory volume in 1 second:forced vital capacity greater than or equal to 0.70) had activity limitations, respiratory symptoms, and exacerbations even though they did not meet the current definition of chronic obstructive pulmonary disease (COPD) (N Engl J Med. 2016;374:1811-21). In the new analysis, further distinctions could be made for patients in this subgroup who also had emphysema on computed tomography (CT).

“Among smokers with preserved lung function, emphysema on CT was associated with reduced activity levels and desaturation on the 6-minute walk test (6MWT),” reported Christian M. Lo Cascio, MD, Columbia University, New York. Compared with smokers with preserved lung function without CT evidence of emphysema, the patients with emphysema on CT did not have more symptoms or exacerbations.

“These and prior findings suggest two distinct but overlapping phenotypes in ever smokers with preserved lung function: an airway disease with respiratory symptoms and frequent exacerbations and emphysema characterized by activity limitation and increased mortality,” said Dr. Lo Cascio.

SPIROMICS, an observational study supported by the National Heart, Lung, and Blood Institute, has enrolled current and former smokers at six centers in the United States to prospectively analyze biomarker, genetic, and clinical data. In the previously published analysis, the focus was on the difference between 849 ever smokers with preserved lung function and 963 patients with mild to moderate COPD. In the data presented by Dr. Lo Cascio, 901 SPIROMICS patients with preserved lung function were analyzed with the focus on the difference between the 66 (7%) who had radiologic evidence of emphysema and the 835 (93%) who had undergone CT indicating that they did not have emphysema.

“Our hypothesis was that the subgroup of patients with emphysema on CT would have lower activity levels, greater desaturation of at least 4% on the 6MWT, more respiratory symptoms, and more exacerbations,” Dr. Lo Cascio reported.

The hypothesis was only half correct. As measured on the activity component of the St. Georges Respiratory Questionnaire, there was about a 10-point (P less than .001) greater reduction in reported activity levels among those with emphysema on CT relative to those without. In addition, the odds ratio (OR) for significant oxygen desaturation, defined as a 4% fall in oxygen saturation of hemoglobin during the 6MWD, was approximately two times greater (P less than .001) for the patients with CT evidence of emphysema.

There were no significant differences between the two groups in walking distance on the 6MWD. Both sets of patients had the same rate of exacerbations and scores on the symptom component of the St. Georges Respiratory Questionnaire, which captures cough, phlegm, wheezing, shortness of breath, and symptom-free days.

Overall, when ever smokers with preserved lung function were subdivided into those with and without CT evidence of emphysema, several similarities were found between the two groups. For those with CT evidence of emphysema and those with no CT evidence of emphysema, mean pack-years of smoking were 43 years and 40 years, respectively, and average body mass indexes were 28.1 and 29.1, respectively. The percentage of patients who had a COPD Assessment Test score of greater than or equal to 10 was 61% among those with CT evidence of emphysema, vs. 50% among those patients without CT evidence of emphysema.

When asked if looking for emphysema on CT in ever smokers with preserved lung function might have clinical utility, Dr. Lo Cascio suggested that it is not yet clear how this information might change management. These data strengthen other evidence from SPIROMICS that ever smokers who do not meet the definition of COPD already have a significant disease burden, he said.

Dr. Lo Cascio reports no relevant financial relationships.

LONDON – Recent evidence of ever smokers having measurable deficits in activity even when lung function is preserved has been further expanded by findings suggesting a different phenotype for patients in this group with radiologic evidence of emphysema, according to data from SPIROMICS (Subpopulations and Intermediate Outcome Measures In COPD Study).

The most recent data were presented at the annual congress of the European Respiratory Society.

Earlier this year, published data drawn from SPIROMICS demonstrated that current and former smokers with preserved lung function (forced expiratory volume in 1 second:forced vital capacity greater than or equal to 0.70) had activity limitations, respiratory symptoms, and exacerbations even though they did not meet the current definition of chronic obstructive pulmonary disease (COPD) (N Engl J Med. 2016;374:1811-21). In the new analysis, further distinctions could be made for patients in this subgroup who also had emphysema on computed tomography (CT).

“Among smokers with preserved lung function, emphysema on CT was associated with reduced activity levels and desaturation on the 6-minute walk test (6MWT),” reported Christian M. Lo Cascio, MD, Columbia University, New York. Compared with smokers with preserved lung function without CT evidence of emphysema, the patients with emphysema on CT did not have more symptoms or exacerbations.

“These and prior findings suggest two distinct but overlapping phenotypes in ever smokers with preserved lung function: an airway disease with respiratory symptoms and frequent exacerbations and emphysema characterized by activity limitation and increased mortality,” said Dr. Lo Cascio.

SPIROMICS, an observational study supported by the National Heart, Lung, and Blood Institute, has enrolled current and former smokers at six centers in the United States to prospectively analyze biomarker, genetic, and clinical data. In the previously published analysis, the focus was on the difference between 849 ever smokers with preserved lung function and 963 patients with mild to moderate COPD. In the data presented by Dr. Lo Cascio, 901 SPIROMICS patients with preserved lung function were analyzed with the focus on the difference between the 66 (7%) who had radiologic evidence of emphysema and the 835 (93%) who had undergone CT indicating that they did not have emphysema.

“Our hypothesis was that the subgroup of patients with emphysema on CT would have lower activity levels, greater desaturation of at least 4% on the 6MWT, more respiratory symptoms, and more exacerbations,” Dr. Lo Cascio reported.

The hypothesis was only half correct. As measured on the activity component of the St. Georges Respiratory Questionnaire, there was about a 10-point (P less than .001) greater reduction in reported activity levels among those with emphysema on CT relative to those without. In addition, the odds ratio (OR) for significant oxygen desaturation, defined as a 4% fall in oxygen saturation of hemoglobin during the 6MWD, was approximately two times greater (P less than .001) for the patients with CT evidence of emphysema.

There were no significant differences between the two groups in walking distance on the 6MWD. Both sets of patients had the same rate of exacerbations and scores on the symptom component of the St. Georges Respiratory Questionnaire, which captures cough, phlegm, wheezing, shortness of breath, and symptom-free days.

Overall, when ever smokers with preserved lung function were subdivided into those with and without CT evidence of emphysema, several similarities were found between the two groups. For those with CT evidence of emphysema and those with no CT evidence of emphysema, mean pack-years of smoking were 43 years and 40 years, respectively, and average body mass indexes were 28.1 and 29.1, respectively. The percentage of patients who had a COPD Assessment Test score of greater than or equal to 10 was 61% among those with CT evidence of emphysema, vs. 50% among those patients without CT evidence of emphysema.

When asked if looking for emphysema on CT in ever smokers with preserved lung function might have clinical utility, Dr. Lo Cascio suggested that it is not yet clear how this information might change management. These data strengthen other evidence from SPIROMICS that ever smokers who do not meet the definition of COPD already have a significant disease burden, he said.

Dr. Lo Cascio reports no relevant financial relationships.

LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.

“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.

In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.

There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.

When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.

The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).

On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.

Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.

According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.

“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.

In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.

These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.

In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.

Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.

[email protected]

LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.

“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.

In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.

There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.

When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.

The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).

On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.

Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.

According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.

“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.

In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.

These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.

In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.

Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.

[email protected]

LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.

“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.

In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.

There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.

When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.

The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).

On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.

Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.

According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.

“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.

In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.

These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.

In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.

Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.

[email protected]

LONDON – Measuring serum levels of the extracellular protein periostin could help identify patients with asthma who have comorbid upper-airway disease, according to research from a late-breaking oral abstract presented at the annual congress of the European Respiratory Society.

Periostin is known to be involved in the pathophysiology of upper-airway disease, linked to both airway remodeling and inflammation. Levels of periostin have been shown to be higher in patients with asthma, allergic rhinitis, and chronic rhinosinusitis than in healthy individuals, and there are data suggesting that it could be linked to severity. However, little is known about whether serum periostin can be used to detect and perhaps monitor upper-airway disease in patients with asthma.

Serum periostin levels were found to be higher in asthma patients with comorbid chronic rhinosinusitis, compared with those with no comorbid upper-airway disease (119.8 vs. 86.3 ng/mL; P = .04).

Levels of periostin in the serum were also significantly higher in asthma patients with chronic rhinosinusitis who also had nasal polyps than in those who did not have nasal polyps (143.3 vs. 94.0 ng/mL; P = .01).

“Serum periostin is a sensitive biomarker for detecting comorbid chronic rhinosinusitis, especially in patients with chronic rhinosinusitis with nasal polyps,” said Dr. Takamitsu Asano, who reported the findings at the meeting. Dr. Asano of Nagoya (Japan) City University Graduate School of Medical Sciences noted that the serum periostin could also reflect the severity of chronic rhinosinusitis in patients with asthma.

“Upper-airway diseases are considered risk factors for the exacerbation and poor control of asthma,” Dr. Asano explained. It is thought, he said, that 40%-50% of patients with asthma have comorbid chronic rhinosinusitis, and 57%-70% have comorbid allergic rhinitis.

Dr. Asano and colleagues at Nagoya City University and Saga (Japan) Medical School recruited 65 patients with stable asthma, with or without comorbid upper-airway disease, between July 2014 and December 2015. Of these patients, 20 had no comorbid upper-airway disease, 22 had rhinitis, 21 had chronic rhinosinusitis, and two had confirmed nasal polyps. Of the 21 patients with chronic rhinosinusitis, 10 had and 11 did not have nasal polyps. Patients’ diagnoses were checked by otorhinolaryngology specialists.

The recruited patients, who were a mean age of 56 years, with an asthma disease duration of 9 years, underwent the following tests: fractional exhaled nitric oxide testing, spirometry, sputum induction, and sinus computed tomography scanning. They also had their blood tested for serum periostin, eosinophils, eotaxin, and immunoglobulin E levels.

Serum periostin levels were found to correlate with the results of fractional exhaled nitric oxide testing, and with blood and sputum eosinophil counts, with respective correlation coefficients of 0.36 (P = .003), 0.35 (P = .005), and 0.44 (P = .004).

In a separate study presented by Dr. Cecile Holweg of Genentech, several patient factors were found to influence the level of serum periostin. Using data from trials of the experimental asthma therapy lebrikizumab and the asthma therapy omalizumab (Xolair), the biologic variability in serum periostin and blood eosinophils was characterized according to patient demographics, asthma severity, concomitant medication use, and comorbidities, including upper-airway diseases.

Multivariate analysis showed that serum periostin levels were higher in patients with nasal polyps and in patients from South America and Asia. Conversely, serum periostin levels were lower in patients with high body mass index and in patients who were current smokers.

Raised eosinophil counts were also seen in patients with nasal polyps and lower eosinophil counts were observed in current smokers.

“These factors should be taken into account when making treatment decisions based on these biomarkers,” Dr. Holweg concluded.

Dr. Asano has received financial support from Novartis, AstraZeneca, Merck Sharp & Dohme, and Eisai Co. Dr. Holweg is an employee of Genentech.

[email protected]

LONDON – Measuring serum levels of the extracellular protein periostin could help identify patients with asthma who have comorbid upper-airway disease, according to research from a late-breaking oral abstract presented at the annual congress of the European Respiratory Society.

Periostin is known to be involved in the pathophysiology of upper-airway disease, linked to both airway remodeling and inflammation. Levels of periostin have been shown to be higher in patients with asthma, allergic rhinitis, and chronic rhinosinusitis than in healthy individuals, and there are data suggesting that it could be linked to severity. However, little is known about whether serum periostin can be used to detect and perhaps monitor upper-airway disease in patients with asthma.

Serum periostin levels were found to be higher in asthma patients with comorbid chronic rhinosinusitis, compared with those with no comorbid upper-airway disease (119.8 vs. 86.3 ng/mL; P = .04).

Levels of periostin in the serum were also significantly higher in asthma patients with chronic rhinosinusitis who also had nasal polyps than in those who did not have nasal polyps (143.3 vs. 94.0 ng/mL; P = .01).

“Serum periostin is a sensitive biomarker for detecting comorbid chronic rhinosinusitis, especially in patients with chronic rhinosinusitis with nasal polyps,” said Dr. Takamitsu Asano, who reported the findings at the meeting. Dr. Asano of Nagoya (Japan) City University Graduate School of Medical Sciences noted that the serum periostin could also reflect the severity of chronic rhinosinusitis in patients with asthma.

“Upper-airway diseases are considered risk factors for the exacerbation and poor control of asthma,” Dr. Asano explained. It is thought, he said, that 40%-50% of patients with asthma have comorbid chronic rhinosinusitis, and 57%-70% have comorbid allergic rhinitis.

Dr. Asano and colleagues at Nagoya City University and Saga (Japan) Medical School recruited 65 patients with stable asthma, with or without comorbid upper-airway disease, between July 2014 and December 2015. Of these patients, 20 had no comorbid upper-airway disease, 22 had rhinitis, 21 had chronic rhinosinusitis, and two had confirmed nasal polyps. Of the 21 patients with chronic rhinosinusitis, 10 had and 11 did not have nasal polyps. Patients’ diagnoses were checked by otorhinolaryngology specialists.

The recruited patients, who were a mean age of 56 years, with an asthma disease duration of 9 years, underwent the following tests: fractional exhaled nitric oxide testing, spirometry, sputum induction, and sinus computed tomography scanning. They also had their blood tested for serum periostin, eosinophils, eotaxin, and immunoglobulin E levels.

Serum periostin levels were found to correlate with the results of fractional exhaled nitric oxide testing, and with blood and sputum eosinophil counts, with respective correlation coefficients of 0.36 (P = .003), 0.35 (P = .005), and 0.44 (P = .004).

In a separate study presented by Dr. Cecile Holweg of Genentech, several patient factors were found to influence the level of serum periostin. Using data from trials of the experimental asthma therapy lebrikizumab and the asthma therapy omalizumab (Xolair), the biologic variability in serum periostin and blood eosinophils was characterized according to patient demographics, asthma severity, concomitant medication use, and comorbidities, including upper-airway diseases.

Multivariate analysis showed that serum periostin levels were higher in patients with nasal polyps and in patients from South America and Asia. Conversely, serum periostin levels were lower in patients with high body mass index and in patients who were current smokers.

Raised eosinophil counts were also seen in patients with nasal polyps and lower eosinophil counts were observed in current smokers.

“These factors should be taken into account when making treatment decisions based on these biomarkers,” Dr. Holweg concluded.

Dr. Asano has received financial support from Novartis, AstraZeneca, Merck Sharp & Dohme, and Eisai Co. Dr. Holweg is an employee of Genentech.

[email protected]

LONDON – Measuring serum levels of the extracellular protein periostin could help identify patients with asthma who have comorbid upper-airway disease, according to research from a late-breaking oral abstract presented at the annual congress of the European Respiratory Society.

Periostin is known to be involved in the pathophysiology of upper-airway disease, linked to both airway remodeling and inflammation. Levels of periostin have been shown to be higher in patients with asthma, allergic rhinitis, and chronic rhinosinusitis than in healthy individuals, and there are data suggesting that it could be linked to severity. However, little is known about whether serum periostin can be used to detect and perhaps monitor upper-airway disease in patients with asthma.

Serum periostin levels were found to be higher in asthma patients with comorbid chronic rhinosinusitis, compared with those with no comorbid upper-airway disease (119.8 vs. 86.3 ng/mL; P = .04).

Levels of periostin in the serum were also significantly higher in asthma patients with chronic rhinosinusitis who also had nasal polyps than in those who did not have nasal polyps (143.3 vs. 94.0 ng/mL; P = .01).

“Serum periostin is a sensitive biomarker for detecting comorbid chronic rhinosinusitis, especially in patients with chronic rhinosinusitis with nasal polyps,” said Dr. Takamitsu Asano, who reported the findings at the meeting. Dr. Asano of Nagoya (Japan) City University Graduate School of Medical Sciences noted that the serum periostin could also reflect the severity of chronic rhinosinusitis in patients with asthma.

“Upper-airway diseases are considered risk factors for the exacerbation and poor control of asthma,” Dr. Asano explained. It is thought, he said, that 40%-50% of patients with asthma have comorbid chronic rhinosinusitis, and 57%-70% have comorbid allergic rhinitis.

Dr. Asano and colleagues at Nagoya City University and Saga (Japan) Medical School recruited 65 patients with stable asthma, with or without comorbid upper-airway disease, between July 2014 and December 2015. Of these patients, 20 had no comorbid upper-airway disease, 22 had rhinitis, 21 had chronic rhinosinusitis, and two had confirmed nasal polyps. Of the 21 patients with chronic rhinosinusitis, 10 had and 11 did not have nasal polyps. Patients’ diagnoses were checked by otorhinolaryngology specialists.

The recruited patients, who were a mean age of 56 years, with an asthma disease duration of 9 years, underwent the following tests: fractional exhaled nitric oxide testing, spirometry, sputum induction, and sinus computed tomography scanning. They also had their blood tested for serum periostin, eosinophils, eotaxin, and immunoglobulin E levels.

Serum periostin levels were found to correlate with the results of fractional exhaled nitric oxide testing, and with blood and sputum eosinophil counts, with respective correlation coefficients of 0.36 (P = .003), 0.35 (P = .005), and 0.44 (P = .004).

In a separate study presented by Dr. Cecile Holweg of Genentech, several patient factors were found to influence the level of serum periostin. Using data from trials of the experimental asthma therapy lebrikizumab and the asthma therapy omalizumab (Xolair), the biologic variability in serum periostin and blood eosinophils was characterized according to patient demographics, asthma severity, concomitant medication use, and comorbidities, including upper-airway diseases.

Multivariate analysis showed that serum periostin levels were higher in patients with nasal polyps and in patients from South America and Asia. Conversely, serum periostin levels were lower in patients with high body mass index and in patients who were current smokers.

Raised eosinophil counts were also seen in patients with nasal polyps and lower eosinophil counts were observed in current smokers.

“These factors should be taken into account when making treatment decisions based on these biomarkers,” Dr. Holweg concluded.

Dr. Asano has received financial support from Novartis, AstraZeneca, Merck Sharp & Dohme, and Eisai Co. Dr. Holweg is an employee of Genentech.

[email protected]