Pulmonary Health Hub

CHICAGO – Antibiotic de-escalation in ICU patients with nosocomial pneumonia in the intensive care unit produced the same clinical outcome – or better – as maintaining broad-spectrum coverage through the treatment course, a study has shown.

Modifying empiric therapy by continuing with narrower-spectrum antibiotics based on culture and antibiotic susceptibility reports not only limits the emergence of multidrug-resistant pathogens, but also reduces resource utilization for the treatment of hospital-acquired pneumonia, ventilator-assisted pneumonia, and health care–associated pneumonia, Chris Destache, Pharm.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The Infectious Diseases Society of America and the American Thoracic Society both advocate early broad-spectrum empiric antibiotics with subsequent streamlining based on the organisms identified and susceptibility patterns in nosocomial pneumonia, but the effect of antibiotic de-escalation on resource utilization, particularly hospital length of stay and cost of hospitalization, has not been examined, Dr. Destache said.

To evaluate the impact of antibiotic de-escalation in the intensive care unit on these resource utilization factors, Dr. Destache of Creighton University in Omaha, Neb., and his colleagues retrospectively studied the charts of patients older than 18 years admitted to the Creighton University Medical Center ICU in 2009 with a presumptive diagnosis of hospital-acquired pneumonia, ventilator-assisted pneumonia, or health care–associated pneumonia, who also had blood or respiratory cultures collected prior to the initiation of antibiotic treatment.

Antibiotic de-escalation was defined as the discontinuation of at least one empiric agent or the change to a narrower-spectrum antibiotic, he said. Patients who received systemic antibacterial, antifungal, or antiviral treatment within 72 hours of their pneumonia diagnosis were excluded from the analysis. The primary study end point was ICU length of stay; secondary end points included total hospital length of stay, in-hospital mortality, and hospitalization costs.

"Culture-negative pneumonias derived the greatest benefit from de-escalation."

Of 378 records identified, 95 patients representing 99 cases of nosocomial pneumonia met the eligibility requirements. "All of the patients had presumptive pneumonia based on [Centers for Disease Control and Prevention] criteria and received broad-spectrum antibiotic therapy based on universal guidelines, and de-escalation was performed in 60 cases," Dr. Destache reported. Universal guidelines call for patients to receive piperacillin-tazobactam, levofloxacin, and vancomycin for at least 24 hours.

Patients in whom the streamlined antibiotic approach was utilized were more likely to be older than those in whom empiric treatment was maintained, with a mean age of 66 years compared with 55.5 years, he said, noting that patients in the de-escalation group were also more likely to have diabetes (38% vs. 18%) and to have cardiovascular disease (38% vs. 15%).

No differences in sequential organ failure assessment scores were observed between the two groups at baseline, although these scores at culture finalization were significantly lower in the de-escalation group, which may have been a factor in the decision to de-escalate, Dr. Destache said.

The ICU length of stay was shorter in the de-escalation group at 9.4 days, compared with 12.8 days in the empiric treatment group, although the difference was not significant. Total length of stay was also shorter, at 15.3 vs. 16.9 days, and hospitalization costs were lower, at $45,640 vs. $60,640, Dr. Destache said at the meeting, sponsored by the American Society for Microbiology. In-hospital mortality was significantly lower in the de-escalation group, at 17% compared with 41%.

Culture was negative in 39 of the de-escalation cases and 18 of the controls, and was positive in 21 of each group, Dr. Destache said. The most common causative pathogens identified in the de-escalation group were methicillin-resistant Staphylococcus aureus (MRSA), followed by methicillin-susceptible S. aureus (MSSA), Pseudomonas aeruginosa, and Streptococcus pneumoniae, he said. In the control group, the most common was MSSA, followed by P. aeruginosa and S. pneumoniae, he said.

In comparing the benefits of antibiotic de-escalation based on culture status, the investigators found that "culture-negative pneumonias derived the greatest benefit from de-escalation," Dr. Destache said. In culture-negative pneumonias, the de-escalation group had an ICU stay of 7.2 days, a total length of stay of 10.4 days, and a mortality of 10%; in the culture-negative control group, ICU stay was 11.9 days, total length of stay was 15.1 days, and mortality was 50%, he said. Culture-positive patients in the de-escalation group stayed in the ICU for 13.6 days and in the hospital for 24.5 days, both of which were statistically similar to the 13.6 days and 18.5 days in the control group; the respective mortality rates were 29% and 33%.

The findings confirm the feasibility and clinical benefit of antimicrobial de-escalation and indicate that the strategy reduces resource utilization, compared with maintaining broad-spectrum coverage, Dr. Destache said. As such, he said, the treatment strategy should be utilized when appropriate as a way to improve antimicrobial stewardship.

Dr. Destache said he had no relevant financial disclosures.

CHICAGO – Antibiotic de-escalation in ICU patients with nosocomial pneumonia in the intensive care unit produced the same clinical outcome – or better – as maintaining broad-spectrum coverage through the treatment course, a study has shown.

Modifying empiric therapy by continuing with narrower-spectrum antibiotics based on culture and antibiotic susceptibility reports not only limits the emergence of multidrug-resistant pathogens, but also reduces resource utilization for the treatment of hospital-acquired pneumonia, ventilator-assisted pneumonia, and health care–associated pneumonia, Chris Destache, Pharm.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The Infectious Diseases Society of America and the American Thoracic Society both advocate early broad-spectrum empiric antibiotics with subsequent streamlining based on the organisms identified and susceptibility patterns in nosocomial pneumonia, but the effect of antibiotic de-escalation on resource utilization, particularly hospital length of stay and cost of hospitalization, has not been examined, Dr. Destache said.

To evaluate the impact of antibiotic de-escalation in the intensive care unit on these resource utilization factors, Dr. Destache of Creighton University in Omaha, Neb., and his colleagues retrospectively studied the charts of patients older than 18 years admitted to the Creighton University Medical Center ICU in 2009 with a presumptive diagnosis of hospital-acquired pneumonia, ventilator-assisted pneumonia, or health care–associated pneumonia, who also had blood or respiratory cultures collected prior to the initiation of antibiotic treatment.

Antibiotic de-escalation was defined as the discontinuation of at least one empiric agent or the change to a narrower-spectrum antibiotic, he said. Patients who received systemic antibacterial, antifungal, or antiviral treatment within 72 hours of their pneumonia diagnosis were excluded from the analysis. The primary study end point was ICU length of stay; secondary end points included total hospital length of stay, in-hospital mortality, and hospitalization costs.

"Culture-negative pneumonias derived the greatest benefit from de-escalation."

Of 378 records identified, 95 patients representing 99 cases of nosocomial pneumonia met the eligibility requirements. "All of the patients had presumptive pneumonia based on [Centers for Disease Control and Prevention] criteria and received broad-spectrum antibiotic therapy based on universal guidelines, and de-escalation was performed in 60 cases," Dr. Destache reported. Universal guidelines call for patients to receive piperacillin-tazobactam, levofloxacin, and vancomycin for at least 24 hours.

Patients in whom the streamlined antibiotic approach was utilized were more likely to be older than those in whom empiric treatment was maintained, with a mean age of 66 years compared with 55.5 years, he said, noting that patients in the de-escalation group were also more likely to have diabetes (38% vs. 18%) and to have cardiovascular disease (38% vs. 15%).

No differences in sequential organ failure assessment scores were observed between the two groups at baseline, although these scores at culture finalization were significantly lower in the de-escalation group, which may have been a factor in the decision to de-escalate, Dr. Destache said.

The ICU length of stay was shorter in the de-escalation group at 9.4 days, compared with 12.8 days in the empiric treatment group, although the difference was not significant. Total length of stay was also shorter, at 15.3 vs. 16.9 days, and hospitalization costs were lower, at $45,640 vs. $60,640, Dr. Destache said at the meeting, sponsored by the American Society for Microbiology. In-hospital mortality was significantly lower in the de-escalation group, at 17% compared with 41%.

Culture was negative in 39 of the de-escalation cases and 18 of the controls, and was positive in 21 of each group, Dr. Destache said. The most common causative pathogens identified in the de-escalation group were methicillin-resistant Staphylococcus aureus (MRSA), followed by methicillin-susceptible S. aureus (MSSA), Pseudomonas aeruginosa, and Streptococcus pneumoniae, he said. In the control group, the most common was MSSA, followed by P. aeruginosa and S. pneumoniae, he said.

In comparing the benefits of antibiotic de-escalation based on culture status, the investigators found that "culture-negative pneumonias derived the greatest benefit from de-escalation," Dr. Destache said. In culture-negative pneumonias, the de-escalation group had an ICU stay of 7.2 days, a total length of stay of 10.4 days, and a mortality of 10%; in the culture-negative control group, ICU stay was 11.9 days, total length of stay was 15.1 days, and mortality was 50%, he said. Culture-positive patients in the de-escalation group stayed in the ICU for 13.6 days and in the hospital for 24.5 days, both of which were statistically similar to the 13.6 days and 18.5 days in the control group; the respective mortality rates were 29% and 33%.

The findings confirm the feasibility and clinical benefit of antimicrobial de-escalation and indicate that the strategy reduces resource utilization, compared with maintaining broad-spectrum coverage, Dr. Destache said. As such, he said, the treatment strategy should be utilized when appropriate as a way to improve antimicrobial stewardship.

Dr. Destache said he had no relevant financial disclosures.

CHICAGO – Antibiotic de-escalation in ICU patients with nosocomial pneumonia in the intensive care unit produced the same clinical outcome – or better – as maintaining broad-spectrum coverage through the treatment course, a study has shown.

Modifying empiric therapy by continuing with narrower-spectrum antibiotics based on culture and antibiotic susceptibility reports not only limits the emergence of multidrug-resistant pathogens, but also reduces resource utilization for the treatment of hospital-acquired pneumonia, ventilator-assisted pneumonia, and health care–associated pneumonia, Chris Destache, Pharm.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The Infectious Diseases Society of America and the American Thoracic Society both advocate early broad-spectrum empiric antibiotics with subsequent streamlining based on the organisms identified and susceptibility patterns in nosocomial pneumonia, but the effect of antibiotic de-escalation on resource utilization, particularly hospital length of stay and cost of hospitalization, has not been examined, Dr. Destache said.

To evaluate the impact of antibiotic de-escalation in the intensive care unit on these resource utilization factors, Dr. Destache of Creighton University in Omaha, Neb., and his colleagues retrospectively studied the charts of patients older than 18 years admitted to the Creighton University Medical Center ICU in 2009 with a presumptive diagnosis of hospital-acquired pneumonia, ventilator-assisted pneumonia, or health care–associated pneumonia, who also had blood or respiratory cultures collected prior to the initiation of antibiotic treatment.

Antibiotic de-escalation was defined as the discontinuation of at least one empiric agent or the change to a narrower-spectrum antibiotic, he said. Patients who received systemic antibacterial, antifungal, or antiviral treatment within 72 hours of their pneumonia diagnosis were excluded from the analysis. The primary study end point was ICU length of stay; secondary end points included total hospital length of stay, in-hospital mortality, and hospitalization costs.

"Culture-negative pneumonias derived the greatest benefit from de-escalation."

Of 378 records identified, 95 patients representing 99 cases of nosocomial pneumonia met the eligibility requirements. "All of the patients had presumptive pneumonia based on [Centers for Disease Control and Prevention] criteria and received broad-spectrum antibiotic therapy based on universal guidelines, and de-escalation was performed in 60 cases," Dr. Destache reported. Universal guidelines call for patients to receive piperacillin-tazobactam, levofloxacin, and vancomycin for at least 24 hours.

Patients in whom the streamlined antibiotic approach was utilized were more likely to be older than those in whom empiric treatment was maintained, with a mean age of 66 years compared with 55.5 years, he said, noting that patients in the de-escalation group were also more likely to have diabetes (38% vs. 18%) and to have cardiovascular disease (38% vs. 15%).

No differences in sequential organ failure assessment scores were observed between the two groups at baseline, although these scores at culture finalization were significantly lower in the de-escalation group, which may have been a factor in the decision to de-escalate, Dr. Destache said.

The ICU length of stay was shorter in the de-escalation group at 9.4 days, compared with 12.8 days in the empiric treatment group, although the difference was not significant. Total length of stay was also shorter, at 15.3 vs. 16.9 days, and hospitalization costs were lower, at $45,640 vs. $60,640, Dr. Destache said at the meeting, sponsored by the American Society for Microbiology. In-hospital mortality was significantly lower in the de-escalation group, at 17% compared with 41%.

Culture was negative in 39 of the de-escalation cases and 18 of the controls, and was positive in 21 of each group, Dr. Destache said. The most common causative pathogens identified in the de-escalation group were methicillin-resistant Staphylococcus aureus (MRSA), followed by methicillin-susceptible S. aureus (MSSA), Pseudomonas aeruginosa, and Streptococcus pneumoniae, he said. In the control group, the most common was MSSA, followed by P. aeruginosa and S. pneumoniae, he said.

In comparing the benefits of antibiotic de-escalation based on culture status, the investigators found that "culture-negative pneumonias derived the greatest benefit from de-escalation," Dr. Destache said. In culture-negative pneumonias, the de-escalation group had an ICU stay of 7.2 days, a total length of stay of 10.4 days, and a mortality of 10%; in the culture-negative control group, ICU stay was 11.9 days, total length of stay was 15.1 days, and mortality was 50%, he said. Culture-positive patients in the de-escalation group stayed in the ICU for 13.6 days and in the hospital for 24.5 days, both of which were statistically similar to the 13.6 days and 18.5 days in the control group; the respective mortality rates were 29% and 33%.

The findings confirm the feasibility and clinical benefit of antimicrobial de-escalation and indicate that the strategy reduces resource utilization, compared with maintaining broad-spectrum coverage, Dr. Destache said. As such, he said, the treatment strategy should be utilized when appropriate as a way to improve antimicrobial stewardship.

Dr. Destache said he had no relevant financial disclosures.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

VANCOUVER, B.C. – Narrowing and loss of small conducting airways precedes the onset of emphysematous destruction and likely accounts for the greatly increased peripheral airway resistance seen in patients with chronic obstructive pulmonary disease, according to new research reported in the Oct. 21 issue of the New England Journal of Medicine.

Previous studies have shown that peripheral airway resistance increases by a factor of 4 to 40 in patients with COPD, with small airways (less than 2 mm in diameter) being the major sites of obstruction. In this study, John E. McDonough, of the James Hogg Research Center at St. Paul’s Hospital, Vancouver, and colleagues used multidetector computed tomography (CT) and microCT to examine the relationship between the numbers and dimensions of small airways and emphysematous destruction in 78 patients who had various stages of COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. The patients had volunteered as part of a study of lung cancer prevention (N. Engl. J. Med. 2011;365:1567-75).

The findings "extend earlier reports by showing that there is both widespread narrowing and loss of smaller conducting airways before the onset of emphysematous destruction in both centrilobular and panlobular emphysema phenotypes of COPD," Mr. McDonough and colleagues said. "This process readily explains the observed increase by a factor of 4 to 40 in small-airway resistance in patients with COPD."

In addition to the 78 patients from the lung cancer prevention study, the researchers collected data on four deceased patients who each donated a lung for transplantation (controls), four patients with centrilobular emphysema who each donated a lung, and eight patients with panlobular emphysema who donated 10 lungs after lung transplantation.

On multidetector CT, the number of airways measuring 2.0-2.5 mm in diameter per lung pair was reduced in patients with GOLD stages 1 and 2 (mild and moderate) disease, compared with controls, Mr. McDonough and colleagues said. There was further reduction in patients with GOLD stages 3 and 4 (severe and very severe) disease.

"The comparison of the results for control samples and those for diseased lungs showed fewer airways measuring 2 to 2.5 mm in both centrilobular and panlobular emphysematous phenotypes of COPD," the researchers said.

The researchers also used microCT to measure the number and cross-sectional area of the small terminal bronchioles, and performed histologic analysis to count the number of small airways per square centimeter and to measure the thickness of airway walls.

On microCT, lungs from patients with the centrilobular emphysematous phenotype of COPD had a reduction of 99.7% in the terminal bronchiolar cross-sectional area per lung, compared with that of the control lungs, and a reduction of 89% in the total number of terminal bronchioles per lung. Explanted lungs from patients with the panlobular emphysema phenotype showed a reduction of 83% in total cross-sectional area and a reduction of 72% in the number of terminal bronchioles, compared with the controls.

Finally, the researchers compared the number and dimensions of terminal bronchioles at different levels of emphysematous destruction. The narrowing and loss of terminal bronchioles preceded emphysematous destruction, they found.

Limitations of microCT include the high radiation dose and the cost of the procedure. Also, the sample design in this study made it difficult to determine whether airways measuring 2.0-2.5 mm in diameter disappeared or "simply narrow[ed] to the point at which the airways were no longer visible at a spatial resolution of approximately 1 mm," the researchers said.

In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, said Dr. Mitzner of the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore.

Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.

Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.

A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute; the Canadian Institute of Health Research–Thoracic Imaging Network of Canada; the Canadian Collaborative Innovative Research Fund; GlaxoSmithKline; and the Lavin Family Supporting Foundation. Three of the authors have received grants, honorarium, service contracts, or travel reimbursement from GSK. The Lavin Family Foundation has provided grants to one author and research support to the institution of another. Dr. Mitzner is on grant review panels for and receives travel expenses from the National Institutes of Health. Further disclosures are available at nejm.org.

BOSTON – A hospital-wide algorithm for diagnosing and managing complicated bacterial pneumonia in children led to a marked cut in unnecessary chest CT examinations and a reduced number of surgical interventions. It also produced better outcomes, with fewer readmissions and no change in average length of stay or vancomycin use.

A key element of the management algorithm, implemented 3 years ago for children with a pleural effusion, empyema, or both complicating community-acquired bacterial pneumonia, was the emphasis on assessing children with ultrasound rather than with CT. This change produced a drop in chest CT examinations in these patients from 60% before the algorithm became hospital policy to 17% after.

The algorithm called for preferentially using ultrasound to assess these cases. During the first 15 months of its use, chest ultrasounds in these patients was performed in 71% of cases, compared with 27% of cases before the algorithm, Dr. Roberta L. DeBiasi said at the meeting.

The preferential use of more ultrasound examinations in children with a pleural-space infection meant that fewer children received the large radiation dose delivered by a CT exam, and the sedation required for CT. While safer, ultrasound also produces better imaging than CT in these patients "to sort out who has a loculated empyema that needs VATS [video-assisted lung surgery] and who has a nonloculated effusion that generally doesn’t need VATS," said Dr. DeBiasi, a pediatric infectious diseases specialist on the staff of Children’s National Medical Center in Washington, D.C.

Creation of a new algorithm for the hospital depended on getting physicians and surgeons from all the divisions and departments involved in managing these children – infectious diseases, surgery, radiology, hospitalists, pulmonology, and emergency department – together to decide on the best management approach and make it hospital policy.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often? The answer was that an ultrasound technician wasn’t available at night in the emergency room." After seeing the data, the radiologists agreed that having ultrasound available 24/7 was important and so arranged it, she said in an interview. The hospital gets on average one or two patients a week with community-acquired bacterial pneumonia complicated by a pleural space infection.

Although no society guidelines existed in November 2008 when the revised algorithm went into effect, last August the Pediatric Infectious Diseases Society and the Infectious Diseases Society of American issued joint recommendations on the management of community-acquired pneumonia in children and included a recommended approach similar to the Children’s National algorithm, Dr. DeBiasi said (Clin. Infect. Dis. 2011 Aug. 30 [doi: 10.1093/cid/cir531]). The only difference was that her hospital’s guidelines are more specific, and guide the staff through the local protocol step by step. For example, the new society recommendations say that either video-assisted lung surgery or fibrinolytic therapy are appropriate options for managing loculated empyema. Because surgeons at Children’s National Medical Center do not use fibrinolytic therapy on these cases, the algorithm specifies VATS only, she said.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often?"

To examine the impact of the algorithm, Dr. DeBiasi and her associates analyzed patient management and outcomes during the 15 months before the revised algorithm went into effect and then during the first 15 months after. The review showed that the 83 patients managed before November 2008 were an average of 6 years old, similar to the 87 patients treated during the first 15 months using the algorithm, who were an average of 5 years old.

The reduced number of CT exams and increased ultrasound use led to a reduction of VATS from 45% of cases before the algorithm to 29% after. Patient outcomes were better – with a "nice," statistically significant drop in readmission rates from 8% before the algorithm to none during the period after – but during both periods, vancomycin use and average length of stay remained constant (35% and 8 days, respectively), Dr. DeBiasi noted.

"Our [inference] is that some patients didn’t need VATS, and so the algorithm reduced unnecessary interventions. These patients were just managed medically," Dr. DeBiasi said. "I think it was the ultrasound that led to less VATS, because ultrasound is better than CT to see who needs VATS and who doesn’t."

Dr. DeBiasi said that she did not have any disclosures.

BOSTON – A hospital-wide algorithm for diagnosing and managing complicated bacterial pneumonia in children led to a marked cut in unnecessary chest CT examinations and a reduced number of surgical interventions. It also produced better outcomes, with fewer readmissions and no change in average length of stay or vancomycin use.

A key element of the management algorithm, implemented 3 years ago for children with a pleural effusion, empyema, or both complicating community-acquired bacterial pneumonia, was the emphasis on assessing children with ultrasound rather than with CT. This change produced a drop in chest CT examinations in these patients from 60% before the algorithm became hospital policy to 17% after.

The algorithm called for preferentially using ultrasound to assess these cases. During the first 15 months of its use, chest ultrasounds in these patients was performed in 71% of cases, compared with 27% of cases before the algorithm, Dr. Roberta L. DeBiasi said at the meeting.

The preferential use of more ultrasound examinations in children with a pleural-space infection meant that fewer children received the large radiation dose delivered by a CT exam, and the sedation required for CT. While safer, ultrasound also produces better imaging than CT in these patients "to sort out who has a loculated empyema that needs VATS [video-assisted lung surgery] and who has a nonloculated effusion that generally doesn’t need VATS," said Dr. DeBiasi, a pediatric infectious diseases specialist on the staff of Children’s National Medical Center in Washington, D.C.

Creation of a new algorithm for the hospital depended on getting physicians and surgeons from all the divisions and departments involved in managing these children – infectious diseases, surgery, radiology, hospitalists, pulmonology, and emergency department – together to decide on the best management approach and make it hospital policy.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often? The answer was that an ultrasound technician wasn’t available at night in the emergency room." After seeing the data, the radiologists agreed that having ultrasound available 24/7 was important and so arranged it, she said in an interview. The hospital gets on average one or two patients a week with community-acquired bacterial pneumonia complicated by a pleural space infection.

Although no society guidelines existed in November 2008 when the revised algorithm went into effect, last August the Pediatric Infectious Diseases Society and the Infectious Diseases Society of American issued joint recommendations on the management of community-acquired pneumonia in children and included a recommended approach similar to the Children’s National algorithm, Dr. DeBiasi said (Clin. Infect. Dis. 2011 Aug. 30 [doi: 10.1093/cid/cir531]). The only difference was that her hospital’s guidelines are more specific, and guide the staff through the local protocol step by step. For example, the new society recommendations say that either video-assisted lung surgery or fibrinolytic therapy are appropriate options for managing loculated empyema. Because surgeons at Children’s National Medical Center do not use fibrinolytic therapy on these cases, the algorithm specifies VATS only, she said.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often?"

To examine the impact of the algorithm, Dr. DeBiasi and her associates analyzed patient management and outcomes during the 15 months before the revised algorithm went into effect and then during the first 15 months after. The review showed that the 83 patients managed before November 2008 were an average of 6 years old, similar to the 87 patients treated during the first 15 months using the algorithm, who were an average of 5 years old.

The reduced number of CT exams and increased ultrasound use led to a reduction of VATS from 45% of cases before the algorithm to 29% after. Patient outcomes were better – with a "nice," statistically significant drop in readmission rates from 8% before the algorithm to none during the period after – but during both periods, vancomycin use and average length of stay remained constant (35% and 8 days, respectively), Dr. DeBiasi noted.

"Our [inference] is that some patients didn’t need VATS, and so the algorithm reduced unnecessary interventions. These patients were just managed medically," Dr. DeBiasi said. "I think it was the ultrasound that led to less VATS, because ultrasound is better than CT to see who needs VATS and who doesn’t."

Dr. DeBiasi said that she did not have any disclosures.

BOSTON – A hospital-wide algorithm for diagnosing and managing complicated bacterial pneumonia in children led to a marked cut in unnecessary chest CT examinations and a reduced number of surgical interventions. It also produced better outcomes, with fewer readmissions and no change in average length of stay or vancomycin use.

A key element of the management algorithm, implemented 3 years ago for children with a pleural effusion, empyema, or both complicating community-acquired bacterial pneumonia, was the emphasis on assessing children with ultrasound rather than with CT. This change produced a drop in chest CT examinations in these patients from 60% before the algorithm became hospital policy to 17% after.

The algorithm called for preferentially using ultrasound to assess these cases. During the first 15 months of its use, chest ultrasounds in these patients was performed in 71% of cases, compared with 27% of cases before the algorithm, Dr. Roberta L. DeBiasi said at the meeting.

The preferential use of more ultrasound examinations in children with a pleural-space infection meant that fewer children received the large radiation dose delivered by a CT exam, and the sedation required for CT. While safer, ultrasound also produces better imaging than CT in these patients "to sort out who has a loculated empyema that needs VATS [video-assisted lung surgery] and who has a nonloculated effusion that generally doesn’t need VATS," said Dr. DeBiasi, a pediatric infectious diseases specialist on the staff of Children’s National Medical Center in Washington, D.C.

Creation of a new algorithm for the hospital depended on getting physicians and surgeons from all the divisions and departments involved in managing these children – infectious diseases, surgery, radiology, hospitalists, pulmonology, and emergency department – together to decide on the best management approach and make it hospital policy.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often? The answer was that an ultrasound technician wasn’t available at night in the emergency room." After seeing the data, the radiologists agreed that having ultrasound available 24/7 was important and so arranged it, she said in an interview. The hospital gets on average one or two patients a week with community-acquired bacterial pneumonia complicated by a pleural space infection.

Although no society guidelines existed in November 2008 when the revised algorithm went into effect, last August the Pediatric Infectious Diseases Society and the Infectious Diseases Society of American issued joint recommendations on the management of community-acquired pneumonia in children and included a recommended approach similar to the Children’s National algorithm, Dr. DeBiasi said (Clin. Infect. Dis. 2011 Aug. 30 [doi: 10.1093/cid/cir531]). The only difference was that her hospital’s guidelines are more specific, and guide the staff through the local protocol step by step. For example, the new society recommendations say that either video-assisted lung surgery or fibrinolytic therapy are appropriate options for managing loculated empyema. Because surgeons at Children’s National Medical Center do not use fibrinolytic therapy on these cases, the algorithm specifies VATS only, she said.

"We asked, don’t you realize there are data that ultrasound is preferable, so why use CT so often?"

To examine the impact of the algorithm, Dr. DeBiasi and her associates analyzed patient management and outcomes during the 15 months before the revised algorithm went into effect and then during the first 15 months after. The review showed that the 83 patients managed before November 2008 were an average of 6 years old, similar to the 87 patients treated during the first 15 months using the algorithm, who were an average of 5 years old.

The reduced number of CT exams and increased ultrasound use led to a reduction of VATS from 45% of cases before the algorithm to 29% after. Patient outcomes were better – with a "nice," statistically significant drop in readmission rates from 8% before the algorithm to none during the period after – but during both periods, vancomycin use and average length of stay remained constant (35% and 8 days, respectively), Dr. DeBiasi noted.

"Our [inference] is that some patients didn’t need VATS, and so the algorithm reduced unnecessary interventions. These patients were just managed medically," Dr. DeBiasi said. "I think it was the ultrasound that led to less VATS, because ultrasound is better than CT to see who needs VATS and who doesn’t."

Dr. DeBiasi said that she did not have any disclosures.

Compared with usual care, the use of annual chest radiographs as a screening tool for lung cancer did not reduce lung cancer mortality in the large, randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

The results dovetail with findings published earlier this year from the NLST (National Lung Screening Trial), which demonstrated a 20% mortality advantage with computed tomography screening vs. chest radiograph screening (N. Engl. J. Med. 2011;365:395-409), according to Dr. Martin M. Oken of the University of Minnesota, Minneapolis, and his colleagues from the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) Project Team.

It follows that CT screening also has a similar advantage over usual care, the investigators said.

In the PLCO trial, the cumulative incidence rates of lung cancer after 13 years of follow-up were 20.1 and 19.2 per 10,000 person-years in the 77,445 trial participants randomized to receive screening with annual chest radiographs and the 77,456 participants assigned to usual care, respectively (relative risk, 1.05). The number of lung cancer deaths was 1,213 in the radiograph group and 1,230 in the usual care group, for cumulative incidence rates of 14.0 and 14.2 per 10,000 person-years, respectively (RR, 0.99), they reported online in the Oct. 26 issue of JAMA.

The lung cancer mortality relative risks were 0.94 for never smokers, 1.02 for former smokers, and 0.99 for current smokers, and for men and women, respectively, they were 1.02 and 0.92.

In a subset of 15,183 intervention patients and 15,138 usual care patients from the PLCO trial who would have met eligibility criteria for the NLST, which was initiated 9 years after the PLCO trial, the cumulative lung cancer incidence rates per 10,000 person-years through 6 years of follow-up were 60.6 and 60.8 in the groups, respectively, the investigators also noted.

Cumulative lung cancer mortality rates in that subset of patients were 36.1 and 38.3 per 10,000 person-years in the radiograph and usual care groups, respectively (RR, 0.94).

"The corresponding [relative risk] for the total PLCO cohort at 6 years was 1.02 for lung cancer incidence and 0.91 for lung cancer mortality," the investigators said.

The PLCO findings, which were published simultaneously with their presentation at CHEST 2011, not only facilitate interpretation of the NLST results, but also "provide important information about the benefits and harms of annual chest radiographic screening," the investigators said, noting that although there were some modest differences between the PLCO and NLST cohorts, "it seems reasonable to consider the chest radiograph vs. usual care comparison in the NLST-eligible cohort in the PLCO to be an adequate surrogate for such a comparison with NLST (JAMA 2011 Oct. 26 [doi:10.1001/jama.2011.1591]).

"As such, the 20% mortality benefit of low-dose spiral CT vs. chest radiograph observed in NLST is likely a good approximation for the mortality benefit that must have been observed of low-dose spiral CT vs. usual care if this latter group had been added to NLST," they said.

PLCO participants were adults aged 55-74 years who were randomly assigned between November 1993 and July 2001 to receive annual screening with posterior-anterior view chest radiographs for 4 years or usual care, which included their usual medical care with no interventions. Adherence to the assigned screening protocol was 86.6% at baseline and 79%-84% at years 1-3. In the usual care group, an estimated 11% (the "contamination rate") underwent chest radiograph screening.

The primary treatment for lung cancer in both groups was similar: The predominant therapy for stage I and II non–small cell lung cancers was resection without chemotherapy, and for stage III or IV non–small cell lung cancers, the predominant therapy was chemotherapy without resection, the investigators noted.

"The randomized groups in the PLCO were comparable at baseline, there was relatively high screening adherence in the intervention group and low contamination in the usual care group, and the treatment distributions across the groups were similar. Therefore, these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with 4 annual chest radiographs," the investigators wrote.

The PLCO Cancer Screening Trial was funded by the National Cancer Institute (NCI) and was also supported by contracts from the NCI’s Division of Cancer Prevention and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics NCI, National Institutes of Health, Department of Health and Human Services. Several authors disclosed potential conflicts of interest, including financial relationships with a number of pharmaceutical companies; the complete list of disclosures is provided in the JAMA article.

Compared with usual care, the use of annual chest radiographs as a screening tool for lung cancer did not reduce lung cancer mortality in the large, randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

The results dovetail with findings published earlier this year from the NLST (National Lung Screening Trial), which demonstrated a 20% mortality advantage with computed tomography screening vs. chest radiograph screening (N. Engl. J. Med. 2011;365:395-409), according to Dr. Martin M. Oken of the University of Minnesota, Minneapolis, and his colleagues from the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) Project Team.

It follows that CT screening also has a similar advantage over usual care, the investigators said.

In the PLCO trial, the cumulative incidence rates of lung cancer after 13 years of follow-up were 20.1 and 19.2 per 10,000 person-years in the 77,445 trial participants randomized to receive screening with annual chest radiographs and the 77,456 participants assigned to usual care, respectively (relative risk, 1.05). The number of lung cancer deaths was 1,213 in the radiograph group and 1,230 in the usual care group, for cumulative incidence rates of 14.0 and 14.2 per 10,000 person-years, respectively (RR, 0.99), they reported online in the Oct. 26 issue of JAMA.

The lung cancer mortality relative risks were 0.94 for never smokers, 1.02 for former smokers, and 0.99 for current smokers, and for men and women, respectively, they were 1.02 and 0.92.

In a subset of 15,183 intervention patients and 15,138 usual care patients from the PLCO trial who would have met eligibility criteria for the NLST, which was initiated 9 years after the PLCO trial, the cumulative lung cancer incidence rates per 10,000 person-years through 6 years of follow-up were 60.6 and 60.8 in the groups, respectively, the investigators also noted.

Cumulative lung cancer mortality rates in that subset of patients were 36.1 and 38.3 per 10,000 person-years in the radiograph and usual care groups, respectively (RR, 0.94).

"The corresponding [relative risk] for the total PLCO cohort at 6 years was 1.02 for lung cancer incidence and 0.91 for lung cancer mortality," the investigators said.

The PLCO findings, which were published simultaneously with their presentation at CHEST 2011, not only facilitate interpretation of the NLST results, but also "provide important information about the benefits and harms of annual chest radiographic screening," the investigators said, noting that although there were some modest differences between the PLCO and NLST cohorts, "it seems reasonable to consider the chest radiograph vs. usual care comparison in the NLST-eligible cohort in the PLCO to be an adequate surrogate for such a comparison with NLST (JAMA 2011 Oct. 26 [doi:10.1001/jama.2011.1591]).

"As such, the 20% mortality benefit of low-dose spiral CT vs. chest radiograph observed in NLST is likely a good approximation for the mortality benefit that must have been observed of low-dose spiral CT vs. usual care if this latter group had been added to NLST," they said.

PLCO participants were adults aged 55-74 years who were randomly assigned between November 1993 and July 2001 to receive annual screening with posterior-anterior view chest radiographs for 4 years or usual care, which included their usual medical care with no interventions. Adherence to the assigned screening protocol was 86.6% at baseline and 79%-84% at years 1-3. In the usual care group, an estimated 11% (the "contamination rate") underwent chest radiograph screening.

The primary treatment for lung cancer in both groups was similar: The predominant therapy for stage I and II non–small cell lung cancers was resection without chemotherapy, and for stage III or IV non–small cell lung cancers, the predominant therapy was chemotherapy without resection, the investigators noted.

"The randomized groups in the PLCO were comparable at baseline, there was relatively high screening adherence in the intervention group and low contamination in the usual care group, and the treatment distributions across the groups were similar. Therefore, these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with 4 annual chest radiographs," the investigators wrote.

The PLCO Cancer Screening Trial was funded by the National Cancer Institute (NCI) and was also supported by contracts from the NCI’s Division of Cancer Prevention and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics NCI, National Institutes of Health, Department of Health and Human Services. Several authors disclosed potential conflicts of interest, including financial relationships with a number of pharmaceutical companies; the complete list of disclosures is provided in the JAMA article.

Compared with usual care, the use of annual chest radiographs as a screening tool for lung cancer did not reduce lung cancer mortality in the large, randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

The results dovetail with findings published earlier this year from the NLST (National Lung Screening Trial), which demonstrated a 20% mortality advantage with computed tomography screening vs. chest radiograph screening (N. Engl. J. Med. 2011;365:395-409), according to Dr. Martin M. Oken of the University of Minnesota, Minneapolis, and his colleagues from the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) Project Team.

It follows that CT screening also has a similar advantage over usual care, the investigators said.

In the PLCO trial, the cumulative incidence rates of lung cancer after 13 years of follow-up were 20.1 and 19.2 per 10,000 person-years in the 77,445 trial participants randomized to receive screening with annual chest radiographs and the 77,456 participants assigned to usual care, respectively (relative risk, 1.05). The number of lung cancer deaths was 1,213 in the radiograph group and 1,230 in the usual care group, for cumulative incidence rates of 14.0 and 14.2 per 10,000 person-years, respectively (RR, 0.99), they reported online in the Oct. 26 issue of JAMA.

The lung cancer mortality relative risks were 0.94 for never smokers, 1.02 for former smokers, and 0.99 for current smokers, and for men and women, respectively, they were 1.02 and 0.92.

In a subset of 15,183 intervention patients and 15,138 usual care patients from the PLCO trial who would have met eligibility criteria for the NLST, which was initiated 9 years after the PLCO trial, the cumulative lung cancer incidence rates per 10,000 person-years through 6 years of follow-up were 60.6 and 60.8 in the groups, respectively, the investigators also noted.

Cumulative lung cancer mortality rates in that subset of patients were 36.1 and 38.3 per 10,000 person-years in the radiograph and usual care groups, respectively (RR, 0.94).

"The corresponding [relative risk] for the total PLCO cohort at 6 years was 1.02 for lung cancer incidence and 0.91 for lung cancer mortality," the investigators said.

The PLCO findings, which were published simultaneously with their presentation at CHEST 2011, not only facilitate interpretation of the NLST results, but also "provide important information about the benefits and harms of annual chest radiographic screening," the investigators said, noting that although there were some modest differences between the PLCO and NLST cohorts, "it seems reasonable to consider the chest radiograph vs. usual care comparison in the NLST-eligible cohort in the PLCO to be an adequate surrogate for such a comparison with NLST (JAMA 2011 Oct. 26 [doi:10.1001/jama.2011.1591]).

"As such, the 20% mortality benefit of low-dose spiral CT vs. chest radiograph observed in NLST is likely a good approximation for the mortality benefit that must have been observed of low-dose spiral CT vs. usual care if this latter group had been added to NLST," they said.

PLCO participants were adults aged 55-74 years who were randomly assigned between November 1993 and July 2001 to receive annual screening with posterior-anterior view chest radiographs for 4 years or usual care, which included their usual medical care with no interventions. Adherence to the assigned screening protocol was 86.6% at baseline and 79%-84% at years 1-3. In the usual care group, an estimated 11% (the "contamination rate") underwent chest radiograph screening.

The primary treatment for lung cancer in both groups was similar: The predominant therapy for stage I and II non–small cell lung cancers was resection without chemotherapy, and for stage III or IV non–small cell lung cancers, the predominant therapy was chemotherapy without resection, the investigators noted.

"The randomized groups in the PLCO were comparable at baseline, there was relatively high screening adherence in the intervention group and low contamination in the usual care group, and the treatment distributions across the groups were similar. Therefore, these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with 4 annual chest radiographs," the investigators wrote.

The PLCO Cancer Screening Trial was funded by the National Cancer Institute (NCI) and was also supported by contracts from the NCI’s Division of Cancer Prevention and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics NCI, National Institutes of Health, Department of Health and Human Services. Several authors disclosed potential conflicts of interest, including financial relationships with a number of pharmaceutical companies; the complete list of disclosures is provided in the JAMA article.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

Unenhanced low-dose CT scans that are used to screen heavy smokers for lung cancer also can identify a substantial percentage of cases of early-stage chronic obstructive pulmonary disease, according to a report in the October 26 issue of JAMA.

The results must still be validated in other cohorts, but "if CT scanning becomes widely adopted for lung cancer screening" it also could be used as a secondary test, outside of the primary and preferred method of screening with pulmonary function testing, to detect chronic obstructive pulmonary disease (COPD) early, wrote Dr. Onno M. Mets of the department of radiology at University Medical Center Utrecht (the Netherlands), and his associates.

"Early diagnosis is important because smoking cessation early in the COPD disease process slows disease progression and decreases morbidity and mortality," the authors noted.

Current CT technology "allows rapid in vivo evaluation of emphysematous parenchymal destruction and small airways dysfunction" by the assessment of air trapping, which "allows information on COPD-related changes to be obtained from CT studies performed for other reasons, such as lung cancer screening," they said.

"We hypothesized that CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD, without the need for obtaining pulmonary function testing," Dr. Mets and his associates wrote.

They assessed a subsample of 1,140 current and former heavy smokers participating in the Dutch Belgian Randomised Lung Cancer Screening Trial who underwent inspiratory and expiratory CT scanning, as well as pulmonary function testing, as part of the protocol for that trial.

"CT-based lung cancer screening in heavy smokers could provide an opportunity to acquire information on the presence of COPD."

All of the study participants were men aged 50-75 years (mean, 63). All had a smoking history of at least 16 cigarettes per day for 25 years or at least 11 cigarettes per day for 30 years – the equivalent of at least 16.5 pack-years.

Based on the results of pulmonary function testing, 437 men had COPD.

The CT scans accurately identified COPD in 274 of those men and gave false-positive results in 85. Thus, CT scans had a sensitivity of 63%, a specificity of 88%, a positive predictive value of 76%, and a negative predictive value of 79% in this cohort, Dr. Mets and his colleagues reported (JAMA 2011;306:1775-81).

The investigators detected COPD in 150 (54%) of 277 men with mild obstruction, 99 (73%) of 135 with moderate obstruction, and 25 of 25 with severe obstruction.

CT was more accurate in identifying COPD among men who were symptomatic than among those who were asymptomatic. This is probably because symptomatic men had more advanced disease, the investigators said.

Separate models for detecting COPD among symptomatic and asymptomatic men did not improve the results.

"Our study may add to the debate about whether and how to implement lung cancer screening for heavy smokers because we have shown that detection of COPD using low-dose screening CT scans may be feasible. Because smokers die not only from lung cancer but also from COPD and cardiovascular disease, the rationale for evaluating lung cancer screening CT scans for additional information may prove important," they wrote.

This study was supported by the Netherlands Organisation for Health Research and Development, Dutch Cancer Society Koningin Wilhelmina Fonds, Stichting Central Fund Reserves of Former Voluntary National Health Service Administration Insurances, Siemens Germany, Rotterdam Oncologic Thoracic Steering Committee, G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and the Erasmus Trust Fund. None of the authors had financial conflicts of interest.

HONOLULU – A large, long-term study suggests that obesity is significantly associated with airway hyperresponsiveness, and therefore it might be a risk factor for asthma.

"There is definitely a relationship between obesity and the risk of having airway hyperresponsiveness, and maybe asthma," lead investigator Dr. Manon Labrecque said during an interview in advance of annual meeting of the American College of Chest Physicians, where the study was presented during a poster session.

"But how is it mediated? What is the explanation? It seems to be related to the mechanical effect of obesity on the volume of the lungs, [but] some other analysis of the data will permit us to better understand," Dr. Labrecque said.

The investigators reviewed the medical records of 17,195 patients with a mean age of 48 years who were referred to the Hôpital du Sacré-Coeur de Montréal, Canada, for confirmation of an asthma diagnosis between 1980 and 2000.

They then analyzed the data in order to classify patients as having obesity class 1 (body mass index of 30-34.9 kg/m²), class 2 (BMI of 35-39.9 kg/m²), or class 3 (BMI more than 40 kg/m²), and compared them with normal-weight patients (those with a BMI between 18.5 and 25 kg/m²). To define airway hyperresponsiveness, the study used a standard criterion: methacholine challenge cutoff of less than 8 mg/mL for causing a 20% fall in FEV₁ (forced expiratory volume in 1 second).

Of the 17,195 patients, 5,623 (33%) demonstrated airway hyperresponsiveness. The relationship between BMI and airway hyperresponsiveness increased in stepwise fashion, from an odds ratio (OR) of 1.15 for obesity class 1 to an OR of 1.46 for obesity class 2 and an OR of 1.50 for obesity class 3.

"We need more analysis to see if the effect of obesity on airway hyperresponsiveness is still there when we correct for lung volume [measures] like the FEV₁," said Dr. Labrecque, a pulmonologist at the hospital who is also affiliated with the department of medicine at the University of Montreal. "If the relation between BMI and airway hyperresponsiveness disappears after this correction, that could mean that it is not the fat itself that is responsible for the risk of asthma, but its mechanical effect on the lung’s volume."

In their poster, the researchers stated that if asthma is added to the list of conditions related to obesity, "then reducing the prevalence of obesity could be expected to produce even greater public health benefits than are currently estimated."

Dr. Labrecque said that she had no relevant financial conflicts to disclose.

HONOLULU – A large, long-term study suggests that obesity is significantly associated with airway hyperresponsiveness, and therefore it might be a risk factor for asthma.

"There is definitely a relationship between obesity and the risk of having airway hyperresponsiveness, and maybe asthma," lead investigator Dr. Manon Labrecque said during an interview in advance of annual meeting of the American College of Chest Physicians, where the study was presented during a poster session.

"But how is it mediated? What is the explanation? It seems to be related to the mechanical effect of obesity on the volume of the lungs, [but] some other analysis of the data will permit us to better understand," Dr. Labrecque said.

The investigators reviewed the medical records of 17,195 patients with a mean age of 48 years who were referred to the Hôpital du Sacré-Coeur de Montréal, Canada, for confirmation of an asthma diagnosis between 1980 and 2000.

They then analyzed the data in order to classify patients as having obesity class 1 (body mass index of 30-34.9 kg/m²), class 2 (BMI of 35-39.9 kg/m²), or class 3 (BMI more than 40 kg/m²), and compared them with normal-weight patients (those with a BMI between 18.5 and 25 kg/m²). To define airway hyperresponsiveness, the study used a standard criterion: methacholine challenge cutoff of less than 8 mg/mL for causing a 20% fall in FEV₁ (forced expiratory volume in 1 second).

Of the 17,195 patients, 5,623 (33%) demonstrated airway hyperresponsiveness. The relationship between BMI and airway hyperresponsiveness increased in stepwise fashion, from an odds ratio (OR) of 1.15 for obesity class 1 to an OR of 1.46 for obesity class 2 and an OR of 1.50 for obesity class 3.

"We need more analysis to see if the effect of obesity on airway hyperresponsiveness is still there when we correct for lung volume [measures] like the FEV₁," said Dr. Labrecque, a pulmonologist at the hospital who is also affiliated with the department of medicine at the University of Montreal. "If the relation between BMI and airway hyperresponsiveness disappears after this correction, that could mean that it is not the fat itself that is responsible for the risk of asthma, but its mechanical effect on the lung’s volume."

In their poster, the researchers stated that if asthma is added to the list of conditions related to obesity, "then reducing the prevalence of obesity could be expected to produce even greater public health benefits than are currently estimated."

Dr. Labrecque said that she had no relevant financial conflicts to disclose.

HONOLULU – A large, long-term study suggests that obesity is significantly associated with airway hyperresponsiveness, and therefore it might be a risk factor for asthma.

"There is definitely a relationship between obesity and the risk of having airway hyperresponsiveness, and maybe asthma," lead investigator Dr. Manon Labrecque said during an interview in advance of annual meeting of the American College of Chest Physicians, where the study was presented during a poster session.

"But how is it mediated? What is the explanation? It seems to be related to the mechanical effect of obesity on the volume of the lungs, [but] some other analysis of the data will permit us to better understand," Dr. Labrecque said.

The investigators reviewed the medical records of 17,195 patients with a mean age of 48 years who were referred to the Hôpital du Sacré-Coeur de Montréal, Canada, for confirmation of an asthma diagnosis between 1980 and 2000.

They then analyzed the data in order to classify patients as having obesity class 1 (body mass index of 30-34.9 kg/m²), class 2 (BMI of 35-39.9 kg/m²), or class 3 (BMI more than 40 kg/m²), and compared them with normal-weight patients (those with a BMI between 18.5 and 25 kg/m²). To define airway hyperresponsiveness, the study used a standard criterion: methacholine challenge cutoff of less than 8 mg/mL for causing a 20% fall in FEV₁ (forced expiratory volume in 1 second).

Of the 17,195 patients, 5,623 (33%) demonstrated airway hyperresponsiveness. The relationship between BMI and airway hyperresponsiveness increased in stepwise fashion, from an odds ratio (OR) of 1.15 for obesity class 1 to an OR of 1.46 for obesity class 2 and an OR of 1.50 for obesity class 3.

"We need more analysis to see if the effect of obesity on airway hyperresponsiveness is still there when we correct for lung volume [measures] like the FEV₁," said Dr. Labrecque, a pulmonologist at the hospital who is also affiliated with the department of medicine at the University of Montreal. "If the relation between BMI and airway hyperresponsiveness disappears after this correction, that could mean that it is not the fat itself that is responsible for the risk of asthma, but its mechanical effect on the lung’s volume."

In their poster, the researchers stated that if asthma is added to the list of conditions related to obesity, "then reducing the prevalence of obesity could be expected to produce even greater public health benefits than are currently estimated."

Dr. Labrecque said that she had no relevant financial conflicts to disclose.

The average annual expenditure on asthma medications for U.S. children rose from $527 million in 1997-1998 to almost $2.5 billion in 2007-2008, an increase of 367%, according to a report from the Agency for Healthcare Research and Quality.

The increase was driven almost entirely by spending on asthma controller medications, which increased by 651% from 1997-1998 to 2007-2008. (See graph, below.) The average annual proportion of children who were treated for asthma rose from 4.7% to 6.1% in the time period studied, the report noted.

Of the four classes of controllers, average annual use among pediatric patients increased for three: Inhaled corticosteroid use went from 15.5% in 1997-1998 to 40.3% in 2007-2008, inhaled long-acting beta-agonist use rose from 3.0% to 13.2%, and leukotriene receptor antagonist use went from 2.9% to 34.1%. The proportion of children using nonsteroidal antiallergy agents dropped from 15.1% in 1997-1998 to 0.6% in 2007-2008, the AHRQ said.

The average annual expenditure on asthma medications for U.S. children rose from $527 million in 1997-1998 to almost $2.5 billion in 2007-2008, an increase of 367%, according to a report from the Agency for Healthcare Research and Quality.

The increase was driven almost entirely by spending on asthma controller medications, which increased by 651% from 1997-1998 to 2007-2008. (See graph, below.) The average annual proportion of children who were treated for asthma rose from 4.7% to 6.1% in the time period studied, the report noted.

Of the four classes of controllers, average annual use among pediatric patients increased for three: Inhaled corticosteroid use went from 15.5% in 1997-1998 to 40.3% in 2007-2008, inhaled long-acting beta-agonist use rose from 3.0% to 13.2%, and leukotriene receptor antagonist use went from 2.9% to 34.1%. The proportion of children using nonsteroidal antiallergy agents dropped from 15.1% in 1997-1998 to 0.6% in 2007-2008, the AHRQ said.

The average annual expenditure on asthma medications for U.S. children rose from $527 million in 1997-1998 to almost $2.5 billion in 2007-2008, an increase of 367%, according to a report from the Agency for Healthcare Research and Quality.

The increase was driven almost entirely by spending on asthma controller medications, which increased by 651% from 1997-1998 to 2007-2008. (See graph, below.) The average annual proportion of children who were treated for asthma rose from 4.7% to 6.1% in the time period studied, the report noted.

Of the four classes of controllers, average annual use among pediatric patients increased for three: Inhaled corticosteroid use went from 15.5% in 1997-1998 to 40.3% in 2007-2008, inhaled long-acting beta-agonist use rose from 3.0% to 13.2%, and leukotriene receptor antagonist use went from 2.9% to 34.1%. The proportion of children using nonsteroidal antiallergy agents dropped from 15.1% in 1997-1998 to 0.6% in 2007-2008, the AHRQ said.

Certain hospitalized adult patients with community-acquired pneumonia (CAP) may require closer monitoring and perhaps intervention because they are at increased risk for acute cardiac events, research suggests.

Eight percent of patients in a prospective cohort study of 3,921 such patients had an acute cardiac event, investigators found. A history of heart disease, hypoalbuminemia, older age, and several other factors conferred an increase in the odds of such events, and a prediction score incorporating these factors had an area under the receiver operating characteristic curve of 0.74.

It may be possible to apply this new information to improve patient outcomes, according to Dr. Carolina Garcia-Vidal, of Bellvitge University Hospital in Barcelona, who presented her research team’s data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"The first thing is you have to recognize which patients are at high risk. And then in that population, maybe you have to do some extra things," she explained in an interview. "Maybe you have to follow [the patient] closer, maybe you have to follow in a special way, such as with a cardiac monitor."

Increased cardiac stress, hypoxemia, and inflammation may all contribute to cardiac events in patients with CAP, Dr. Garcia-Vidal noted. Regarding the last, "if you are able to relate these events with a proinflammatory effect, maybe you can do something to modulate this inflammatory [state]. I think that’s the future."

The investigators prospectively studied 3,921 adult inpatients treated in the hospital between 1995 and 2010 who had CAP and did not have severe immunosuppression.

Overall, 8% experienced at least one acute cardiac event (myocardial infarction, new or worsening arrhythmia, and/or new or worsening congestive heart failure) during their hospital stay, according to results reported in a poster session at the conference, which was sponsored by the American Society for Microbiology.

"These patients have a mortality that is very high," Dr. Garcia-Vidal pointed out. In fact, they were about three times more likely to die within 30 days than their event-free counterparts (19% vs. 6%).

In a multivariate analysis, patients had significantly higher odds of acute cardiac events if they were older than 65 years or had heart disease, kidney disease, tachycardia, hypotension, hypoalbuminemia, multilobar pneumonia, or pneumococcal pneumonia, with odds ratios ranging from 1.37 to 3.03.

The factors were combined to create a 9-point score, which had an area under the receiver operating characteristic curve of 0.74 for predicting acute cardiac events. The rate of such events was 19% among patients falling into a high-risk group, defined as having a score of 3 or higher.

The investigators plan to validate the model in another patient population, according to Dr. Garcia-Vidal, whose team reported having no relevant conflicts of interest.

Certain hospitalized adult patients with community-acquired pneumonia (CAP) may require closer monitoring and perhaps intervention because they are at increased risk for acute cardiac events, research suggests.

Eight percent of patients in a prospective cohort study of 3,921 such patients had an acute cardiac event, investigators found. A history of heart disease, hypoalbuminemia, older age, and several other factors conferred an increase in the odds of such events, and a prediction score incorporating these factors had an area under the receiver operating characteristic curve of 0.74.

It may be possible to apply this new information to improve patient outcomes, according to Dr. Carolina Garcia-Vidal, of Bellvitge University Hospital in Barcelona, who presented her research team’s data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"The first thing is you have to recognize which patients are at high risk. And then in that population, maybe you have to do some extra things," she explained in an interview. "Maybe you have to follow [the patient] closer, maybe you have to follow in a special way, such as with a cardiac monitor."

Increased cardiac stress, hypoxemia, and inflammation may all contribute to cardiac events in patients with CAP, Dr. Garcia-Vidal noted. Regarding the last, "if you are able to relate these events with a proinflammatory effect, maybe you can do something to modulate this inflammatory [state]. I think that’s the future."

The investigators prospectively studied 3,921 adult inpatients treated in the hospital between 1995 and 2010 who had CAP and did not have severe immunosuppression.

Overall, 8% experienced at least one acute cardiac event (myocardial infarction, new or worsening arrhythmia, and/or new or worsening congestive heart failure) during their hospital stay, according to results reported in a poster session at the conference, which was sponsored by the American Society for Microbiology.

"These patients have a mortality that is very high," Dr. Garcia-Vidal pointed out. In fact, they were about three times more likely to die within 30 days than their event-free counterparts (19% vs. 6%).

In a multivariate analysis, patients had significantly higher odds of acute cardiac events if they were older than 65 years or had heart disease, kidney disease, tachycardia, hypotension, hypoalbuminemia, multilobar pneumonia, or pneumococcal pneumonia, with odds ratios ranging from 1.37 to 3.03.

The factors were combined to create a 9-point score, which had an area under the receiver operating characteristic curve of 0.74 for predicting acute cardiac events. The rate of such events was 19% among patients falling into a high-risk group, defined as having a score of 3 or higher.

The investigators plan to validate the model in another patient population, according to Dr. Garcia-Vidal, whose team reported having no relevant conflicts of interest.

Certain hospitalized adult patients with community-acquired pneumonia (CAP) may require closer monitoring and perhaps intervention because they are at increased risk for acute cardiac events, research suggests.

Eight percent of patients in a prospective cohort study of 3,921 such patients had an acute cardiac event, investigators found. A history of heart disease, hypoalbuminemia, older age, and several other factors conferred an increase in the odds of such events, and a prediction score incorporating these factors had an area under the receiver operating characteristic curve of 0.74.

It may be possible to apply this new information to improve patient outcomes, according to Dr. Carolina Garcia-Vidal, of Bellvitge University Hospital in Barcelona, who presented her research team’s data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"The first thing is you have to recognize which patients are at high risk. And then in that population, maybe you have to do some extra things," she explained in an interview. "Maybe you have to follow [the patient] closer, maybe you have to follow in a special way, such as with a cardiac monitor."

Increased cardiac stress, hypoxemia, and inflammation may all contribute to cardiac events in patients with CAP, Dr. Garcia-Vidal noted. Regarding the last, "if you are able to relate these events with a proinflammatory effect, maybe you can do something to modulate this inflammatory [state]. I think that’s the future."

The investigators prospectively studied 3,921 adult inpatients treated in the hospital between 1995 and 2010 who had CAP and did not have severe immunosuppression.

Overall, 8% experienced at least one acute cardiac event (myocardial infarction, new or worsening arrhythmia, and/or new or worsening congestive heart failure) during their hospital stay, according to results reported in a poster session at the conference, which was sponsored by the American Society for Microbiology.

"These patients have a mortality that is very high," Dr. Garcia-Vidal pointed out. In fact, they were about three times more likely to die within 30 days than their event-free counterparts (19% vs. 6%).

In a multivariate analysis, patients had significantly higher odds of acute cardiac events if they were older than 65 years or had heart disease, kidney disease, tachycardia, hypotension, hypoalbuminemia, multilobar pneumonia, or pneumococcal pneumonia, with odds ratios ranging from 1.37 to 3.03.

The factors were combined to create a 9-point score, which had an area under the receiver operating characteristic curve of 0.74 for predicting acute cardiac events. The rate of such events was 19% among patients falling into a high-risk group, defined as having a score of 3 or higher.

The investigators plan to validate the model in another patient population, according to Dr. Garcia-Vidal, whose team reported having no relevant conflicts of interest.