Pulmonary Health Hub

HONOLULU – Current interventions for chronic obstructive pulmonary disease leave many patients with unmet needs, according to Dr. Nicola A. Hanania.

"We know from large clinical trials that current pharmacotherapies do not change the natural history of COPD, and many patients remain symptomatic with current therapies," Dr. Hanania, director of the asthma clinical research center at Baylor College of Medicine, Houston, said at the annual meeting of the American College of Chest Physicians.

Inadequate adherence to therapy "is a major cause of poor clinical outcomes in the treatment of COPD," he said. The cost, compliance, and safety of certain agents are issues "that we cannot ignore."

When considering a therapy for COPD, clinicians should factor in components of COPD beyond bronchoconstriction, he advised, including mucociliary dysfunction, structural changes in the airway and the lung, systemic components, and airway inflammation. "We also have to look at outcomes other than lung function including exacerbations, activity limitation, and symptoms of dyspnea," he said. "We are no more satisfied with just a drug that improves lung function but does nothing for the patient-reported outcomes."

Dr. Hanania’s "wish list" for an ideal COPD therapeutic option in the future is one that addresses the multiple components and phenotypes of COPD. He said he would like to see drugs that blunt proinflammatory cells and molecules known to be involved in COPD. "We’d also like to see drugs that could modify the disease progression and comorbid conditions," he said. Such drugs, he continued, should be well tolerated and compatible with other therapies for COPD and comorbid conditions, be simple to administer, and have the potential to improve patient adherence, he added.

Treatment approaches being studied include novel formulations of existing medications, such as the combination of ultralong-acting beta-2 agonists and long-acting antimuscarinics. Among the agents that are the most promising on this front, he said, are indacaterol plus glycopyrronium (QVA-149) and vilanterol plus GSK-573719.

Other agents in development include bifunctional muscarinic antagonist–beta-2 agonists such as GSK-961081 and THRX-200495 as well as combinations of once-daily long-acting beta-2 agonists and inhaled corticosteroids, including formoterol and mometasone (MFF258) and vilanterol and fluticasone (Relovair).

However, perhaps the most promising pharmacotherapies will be novel agents aimed at reducing local and systemic inflammation. "We know that COPD is an inflammatory disease, so we need drugs that can target inflammation right from the very beginning," Dr. Hanania explained. "Inhaled steroids are important, but they’re not as effective in COPD as they are in asthma."

Phosphodiesterase type 4 inhibitors are currently being studied in COPD. These agents reduce the activity of neutrophils, macrophages, and CD8-positive T-lymphocytes, as well as the expression of cytokines and other inflammatory mediators. Currently, the only phosphodiesterase type 4 inhibitor approved in the United States for use in patients with COPD is roflumilast (Daliresp). Several others are in development.

"We know from large clinical trials that current pharmaco-therapies do not change the natural history of COPD."

Because they target airway inflammation, p38 mitogen-activated protein kinase inhibitors are also being studied in COPD patients. However, so far clinical trials have found potential problems related to systemic side effects and toxicity, "indicating that it is probably necessary to deliver these drugs by inhalation to reduce systemic exposure," Dr. Hanania said.

He concluded his presentation by noting that certain medications used to treat comorbidities in COPD may have beneficial effects on COPD outcomes. These include statins, ACE inhibitors, beta-blockers, peroxisome proliferator–activated receptor agonists, and macrolides. The National Heart, Lung, and Blood Institute COPD Clinical Research Network is currently conducting a prospective randomized controlled trial in 1,126 patients with severe COPD randomized to daily simvastatin (40 mg) vs. placebo for at least 1 year. The primary outcome is exacerbation of COPD. The secondary outcomes include change in forced expiratory volume in 1 second (FEV₁), St. George’s Respiratory Questionnaire responses, 6-minute walk test results, BODE Index score, a combined cardiovascular end point, and serum inflammatory biomarker levels. Furthermore, a recent study showed that daily azithromycin significantly reduced exacerbations in high-risk patients.

Dr. Hanania disclosed that he has received grant support from the National Institutes of Health, the American Lung Association, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Sunovion, Novartis, Pfizer, and Forest Pharmaceuticals. He also serves as a consultant for GSK, Dey Pharmaceuticals, Sunovion, Pfizer, and Forest, and is a member of the speakers bureau for GSK, BI, AstraZeneca, and Forest.

HONOLULU – Current interventions for chronic obstructive pulmonary disease leave many patients with unmet needs, according to Dr. Nicola A. Hanania.

"We know from large clinical trials that current pharmacotherapies do not change the natural history of COPD, and many patients remain symptomatic with current therapies," Dr. Hanania, director of the asthma clinical research center at Baylor College of Medicine, Houston, said at the annual meeting of the American College of Chest Physicians.

Inadequate adherence to therapy "is a major cause of poor clinical outcomes in the treatment of COPD," he said. The cost, compliance, and safety of certain agents are issues "that we cannot ignore."

When considering a therapy for COPD, clinicians should factor in components of COPD beyond bronchoconstriction, he advised, including mucociliary dysfunction, structural changes in the airway and the lung, systemic components, and airway inflammation. "We also have to look at outcomes other than lung function including exacerbations, activity limitation, and symptoms of dyspnea," he said. "We are no more satisfied with just a drug that improves lung function but does nothing for the patient-reported outcomes."

Dr. Hanania’s "wish list" for an ideal COPD therapeutic option in the future is one that addresses the multiple components and phenotypes of COPD. He said he would like to see drugs that blunt proinflammatory cells and molecules known to be involved in COPD. "We’d also like to see drugs that could modify the disease progression and comorbid conditions," he said. Such drugs, he continued, should be well tolerated and compatible with other therapies for COPD and comorbid conditions, be simple to administer, and have the potential to improve patient adherence, he added.

Treatment approaches being studied include novel formulations of existing medications, such as the combination of ultralong-acting beta-2 agonists and long-acting antimuscarinics. Among the agents that are the most promising on this front, he said, are indacaterol plus glycopyrronium (QVA-149) and vilanterol plus GSK-573719.

Other agents in development include bifunctional muscarinic antagonist–beta-2 agonists such as GSK-961081 and THRX-200495 as well as combinations of once-daily long-acting beta-2 agonists and inhaled corticosteroids, including formoterol and mometasone (MFF258) and vilanterol and fluticasone (Relovair).

However, perhaps the most promising pharmacotherapies will be novel agents aimed at reducing local and systemic inflammation. "We know that COPD is an inflammatory disease, so we need drugs that can target inflammation right from the very beginning," Dr. Hanania explained. "Inhaled steroids are important, but they’re not as effective in COPD as they are in asthma."

Phosphodiesterase type 4 inhibitors are currently being studied in COPD. These agents reduce the activity of neutrophils, macrophages, and CD8-positive T-lymphocytes, as well as the expression of cytokines and other inflammatory mediators. Currently, the only phosphodiesterase type 4 inhibitor approved in the United States for use in patients with COPD is roflumilast (Daliresp). Several others are in development.

"We know from large clinical trials that current pharmaco-therapies do not change the natural history of COPD."

Because they target airway inflammation, p38 mitogen-activated protein kinase inhibitors are also being studied in COPD patients. However, so far clinical trials have found potential problems related to systemic side effects and toxicity, "indicating that it is probably necessary to deliver these drugs by inhalation to reduce systemic exposure," Dr. Hanania said.

He concluded his presentation by noting that certain medications used to treat comorbidities in COPD may have beneficial effects on COPD outcomes. These include statins, ACE inhibitors, beta-blockers, peroxisome proliferator–activated receptor agonists, and macrolides. The National Heart, Lung, and Blood Institute COPD Clinical Research Network is currently conducting a prospective randomized controlled trial in 1,126 patients with severe COPD randomized to daily simvastatin (40 mg) vs. placebo for at least 1 year. The primary outcome is exacerbation of COPD. The secondary outcomes include change in forced expiratory volume in 1 second (FEV₁), St. George’s Respiratory Questionnaire responses, 6-minute walk test results, BODE Index score, a combined cardiovascular end point, and serum inflammatory biomarker levels. Furthermore, a recent study showed that daily azithromycin significantly reduced exacerbations in high-risk patients.

Dr. Hanania disclosed that he has received grant support from the National Institutes of Health, the American Lung Association, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Sunovion, Novartis, Pfizer, and Forest Pharmaceuticals. He also serves as a consultant for GSK, Dey Pharmaceuticals, Sunovion, Pfizer, and Forest, and is a member of the speakers bureau for GSK, BI, AstraZeneca, and Forest.

HONOLULU – Current interventions for chronic obstructive pulmonary disease leave many patients with unmet needs, according to Dr. Nicola A. Hanania.

"We know from large clinical trials that current pharmacotherapies do not change the natural history of COPD, and many patients remain symptomatic with current therapies," Dr. Hanania, director of the asthma clinical research center at Baylor College of Medicine, Houston, said at the annual meeting of the American College of Chest Physicians.

Inadequate adherence to therapy "is a major cause of poor clinical outcomes in the treatment of COPD," he said. The cost, compliance, and safety of certain agents are issues "that we cannot ignore."

When considering a therapy for COPD, clinicians should factor in components of COPD beyond bronchoconstriction, he advised, including mucociliary dysfunction, structural changes in the airway and the lung, systemic components, and airway inflammation. "We also have to look at outcomes other than lung function including exacerbations, activity limitation, and symptoms of dyspnea," he said. "We are no more satisfied with just a drug that improves lung function but does nothing for the patient-reported outcomes."

Dr. Hanania’s "wish list" for an ideal COPD therapeutic option in the future is one that addresses the multiple components and phenotypes of COPD. He said he would like to see drugs that blunt proinflammatory cells and molecules known to be involved in COPD. "We’d also like to see drugs that could modify the disease progression and comorbid conditions," he said. Such drugs, he continued, should be well tolerated and compatible with other therapies for COPD and comorbid conditions, be simple to administer, and have the potential to improve patient adherence, he added.

Treatment approaches being studied include novel formulations of existing medications, such as the combination of ultralong-acting beta-2 agonists and long-acting antimuscarinics. Among the agents that are the most promising on this front, he said, are indacaterol plus glycopyrronium (QVA-149) and vilanterol plus GSK-573719.

Other agents in development include bifunctional muscarinic antagonist–beta-2 agonists such as GSK-961081 and THRX-200495 as well as combinations of once-daily long-acting beta-2 agonists and inhaled corticosteroids, including formoterol and mometasone (MFF258) and vilanterol and fluticasone (Relovair).

However, perhaps the most promising pharmacotherapies will be novel agents aimed at reducing local and systemic inflammation. "We know that COPD is an inflammatory disease, so we need drugs that can target inflammation right from the very beginning," Dr. Hanania explained. "Inhaled steroids are important, but they’re not as effective in COPD as they are in asthma."

Phosphodiesterase type 4 inhibitors are currently being studied in COPD. These agents reduce the activity of neutrophils, macrophages, and CD8-positive T-lymphocytes, as well as the expression of cytokines and other inflammatory mediators. Currently, the only phosphodiesterase type 4 inhibitor approved in the United States for use in patients with COPD is roflumilast (Daliresp). Several others are in development.

"We know from large clinical trials that current pharmaco-therapies do not change the natural history of COPD."

Because they target airway inflammation, p38 mitogen-activated protein kinase inhibitors are also being studied in COPD patients. However, so far clinical trials have found potential problems related to systemic side effects and toxicity, "indicating that it is probably necessary to deliver these drugs by inhalation to reduce systemic exposure," Dr. Hanania said.

He concluded his presentation by noting that certain medications used to treat comorbidities in COPD may have beneficial effects on COPD outcomes. These include statins, ACE inhibitors, beta-blockers, peroxisome proliferator–activated receptor agonists, and macrolides. The National Heart, Lung, and Blood Institute COPD Clinical Research Network is currently conducting a prospective randomized controlled trial in 1,126 patients with severe COPD randomized to daily simvastatin (40 mg) vs. placebo for at least 1 year. The primary outcome is exacerbation of COPD. The secondary outcomes include change in forced expiratory volume in 1 second (FEV₁), St. George’s Respiratory Questionnaire responses, 6-minute walk test results, BODE Index score, a combined cardiovascular end point, and serum inflammatory biomarker levels. Furthermore, a recent study showed that daily azithromycin significantly reduced exacerbations in high-risk patients.

Dr. Hanania disclosed that he has received grant support from the National Institutes of Health, the American Lung Association, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Sunovion, Novartis, Pfizer, and Forest Pharmaceuticals. He also serves as a consultant for GSK, Dey Pharmaceuticals, Sunovion, Pfizer, and Forest, and is a member of the speakers bureau for GSK, BI, AstraZeneca, and Forest.

HONOLULU – Acute worsening is an important part of the natural history of many interstitial lung diseases, especially idiopathic pulmonary fibrosis.

But the roots of acute worsening in interstitial lung disease (ILD) are not fully understood, Dr. Harold R. Collard said at the annual meeting of the American College of Chest Physicians.

"A lot of what’s known in the medical literature comes from patients with idiopathic pulmonary fibrosis [IPF]," said Dr. Collard, who directs the interstitial lung disease program at the University of California, San Francisco. "I think it’s an open question whether that can be extrapolated to patients with other forms of ILD or not. The course of many ILDs – certainly IPF – is unpredictable; it’s not always a linear decline," he continued. "This is an important shift in how we think about the disease – to recognize that this is the case for many patients."

According to a survey of academic pulmonologists, 88% of respondents reported that acute exacerbations in ILD patients occur "sometimes" or "frequently," while 92% of respondents reported that exacerbations were "sometimes" or "frequently" fatal (Respir. Med. 2007;101:2011-6).

If these are not fatal, they often leave patients significantly worse than they were before, unlike exacerbations in other forms of lung disease, said Dr. Collard, who was the survey’s lead investigator.

Potential causes of acute worsening include infection, aspiration, myocardial infarction, pulmonary embolism, pneumothorax, and heart failure, as well as idiopathic causes. Acute worsening has not been studied in all ILDs, but it has been most closely studied in IPF. In Dr. Collard’s opinion, the best data on acute worsening in IPF come from a Korean cohort study of 461 patients with IPF who were followed longitudinally (Eur. Resp. J. 2011;37:356-63). The researchers divided patients into two groups: those with respiratory deterioration (defined as acute worsening with radiographic abnormalities) and those with acute exacerbation (defined as acute worsening in the absence of an identifiable etiology).

The researchers found that the 1-year incidence of respiratory deterioration was 23%, "which is higher than a lot of us have taken from clinical trials," Dr. Collard said. Of these cases, 55% were idiopathic, while the remainder had known causes that included infection and heart failure.

"These idiopathic acute worsenings, as defined in this study, are what we call acute exacerbation," Dr. Collard noted. "In IPF, acute exacerbation has a specific connotation compared with asthma or [chronic obstructive pulmonary disease]. It’s an idiopathic acute worsening."

The median survival among patients with acute exacerbation of IPF was 2.2 months from the onset of exacerbation. "This is a highly morbid and fatal condition," he said.

Dr. Collard led a panel of experts that established criteria for acute exacerbations of IPF (Am. J. Respir. Crit. Care Med. 2007;176:636-43). The criteria include previous or concurrent diagnosis of IPF, unexplained worsening or development of dyspnea over a period of 30 days or less, new bilateral ground glass and/or consolidation superimposed on a usual interstitial pneumonitis pattern on high-resolution CT, no microbiologic evidence of respiratory infection by endotracheal aspirate or bronchoalveolar lavage, and exclusion of other known causes of acute worsening.

According to the Korean IPF cohort study, significant risk factors for acute exacerbation include never having smoked tobacco and having a low forced vital capacity (FVC). "The higher your FVC, the lower your risk of acute exacerbation," Dr. Collard said. "That makes sense, [but] the protective effect of smoking is hard to explain."

He acknowledged that certain aspects of acute exacerbation remain elusive. "Does exacerbation actually represent an abrupt acceleration of the underlying disease process, or is it a manifestation of an occult secondary complication such as an infection that we’re missing because of the limitations of our clinical assessment?" he asked.

Researchers who conducted a test of gene expression profiling in this patient population found no differences in the global expression pattern between patients with stable IPF and those with acute exacerbation (Am. J. Respir. Crit. Care Med. 2009;180:167-75). "They did find evidence of enhanced alveolar epithelial cell activity," Dr. Collard said. "That was the main predominant pattern."

A study of biomarkers conducted by Dr. Collard and his associates yielded similar findings (Am. J. Physiol. Lung Cell Mol. Physiol. 2010;299:L3-7).

Dr. Collard hypothesized that acute exacerbation of IPF represents a primary acceleration of IPF in the setting of acute lung stress. "This stress may be minor, at a level that would not cause clinical disease in a normal lung," he said. Potential sources of stress include infection, occult aspiration, interventions, and drugs.

Dr. Collard disclosed that he receives research funding from the National Institutes of Health, the University of California, Boehringer Ingelheim, and Genentech. He also receives consulting fees from Fibrogen, Gilead, InterMune, and Onyx.

HONOLULU – Acute worsening is an important part of the natural history of many interstitial lung diseases, especially idiopathic pulmonary fibrosis.

But the roots of acute worsening in interstitial lung disease (ILD) are not fully understood, Dr. Harold R. Collard said at the annual meeting of the American College of Chest Physicians.

"A lot of what’s known in the medical literature comes from patients with idiopathic pulmonary fibrosis [IPF]," said Dr. Collard, who directs the interstitial lung disease program at the University of California, San Francisco. "I think it’s an open question whether that can be extrapolated to patients with other forms of ILD or not. The course of many ILDs – certainly IPF – is unpredictable; it’s not always a linear decline," he continued. "This is an important shift in how we think about the disease – to recognize that this is the case for many patients."

According to a survey of academic pulmonologists, 88% of respondents reported that acute exacerbations in ILD patients occur "sometimes" or "frequently," while 92% of respondents reported that exacerbations were "sometimes" or "frequently" fatal (Respir. Med. 2007;101:2011-6).

If these are not fatal, they often leave patients significantly worse than they were before, unlike exacerbations in other forms of lung disease, said Dr. Collard, who was the survey’s lead investigator.

Potential causes of acute worsening include infection, aspiration, myocardial infarction, pulmonary embolism, pneumothorax, and heart failure, as well as idiopathic causes. Acute worsening has not been studied in all ILDs, but it has been most closely studied in IPF. In Dr. Collard’s opinion, the best data on acute worsening in IPF come from a Korean cohort study of 461 patients with IPF who were followed longitudinally (Eur. Resp. J. 2011;37:356-63). The researchers divided patients into two groups: those with respiratory deterioration (defined as acute worsening with radiographic abnormalities) and those with acute exacerbation (defined as acute worsening in the absence of an identifiable etiology).

The researchers found that the 1-year incidence of respiratory deterioration was 23%, "which is higher than a lot of us have taken from clinical trials," Dr. Collard said. Of these cases, 55% were idiopathic, while the remainder had known causes that included infection and heart failure.

"These idiopathic acute worsenings, as defined in this study, are what we call acute exacerbation," Dr. Collard noted. "In IPF, acute exacerbation has a specific connotation compared with asthma or [chronic obstructive pulmonary disease]. It’s an idiopathic acute worsening."

The median survival among patients with acute exacerbation of IPF was 2.2 months from the onset of exacerbation. "This is a highly morbid and fatal condition," he said.

Dr. Collard led a panel of experts that established criteria for acute exacerbations of IPF (Am. J. Respir. Crit. Care Med. 2007;176:636-43). The criteria include previous or concurrent diagnosis of IPF, unexplained worsening or development of dyspnea over a period of 30 days or less, new bilateral ground glass and/or consolidation superimposed on a usual interstitial pneumonitis pattern on high-resolution CT, no microbiologic evidence of respiratory infection by endotracheal aspirate or bronchoalveolar lavage, and exclusion of other known causes of acute worsening.

According to the Korean IPF cohort study, significant risk factors for acute exacerbation include never having smoked tobacco and having a low forced vital capacity (FVC). "The higher your FVC, the lower your risk of acute exacerbation," Dr. Collard said. "That makes sense, [but] the protective effect of smoking is hard to explain."

He acknowledged that certain aspects of acute exacerbation remain elusive. "Does exacerbation actually represent an abrupt acceleration of the underlying disease process, or is it a manifestation of an occult secondary complication such as an infection that we’re missing because of the limitations of our clinical assessment?" he asked.

Researchers who conducted a test of gene expression profiling in this patient population found no differences in the global expression pattern between patients with stable IPF and those with acute exacerbation (Am. J. Respir. Crit. Care Med. 2009;180:167-75). "They did find evidence of enhanced alveolar epithelial cell activity," Dr. Collard said. "That was the main predominant pattern."

A study of biomarkers conducted by Dr. Collard and his associates yielded similar findings (Am. J. Physiol. Lung Cell Mol. Physiol. 2010;299:L3-7).

Dr. Collard hypothesized that acute exacerbation of IPF represents a primary acceleration of IPF in the setting of acute lung stress. "This stress may be minor, at a level that would not cause clinical disease in a normal lung," he said. Potential sources of stress include infection, occult aspiration, interventions, and drugs.

Dr. Collard disclosed that he receives research funding from the National Institutes of Health, the University of California, Boehringer Ingelheim, and Genentech. He also receives consulting fees from Fibrogen, Gilead, InterMune, and Onyx.

HONOLULU – Acute worsening is an important part of the natural history of many interstitial lung diseases, especially idiopathic pulmonary fibrosis.

But the roots of acute worsening in interstitial lung disease (ILD) are not fully understood, Dr. Harold R. Collard said at the annual meeting of the American College of Chest Physicians.

"A lot of what’s known in the medical literature comes from patients with idiopathic pulmonary fibrosis [IPF]," said Dr. Collard, who directs the interstitial lung disease program at the University of California, San Francisco. "I think it’s an open question whether that can be extrapolated to patients with other forms of ILD or not. The course of many ILDs – certainly IPF – is unpredictable; it’s not always a linear decline," he continued. "This is an important shift in how we think about the disease – to recognize that this is the case for many patients."

According to a survey of academic pulmonologists, 88% of respondents reported that acute exacerbations in ILD patients occur "sometimes" or "frequently," while 92% of respondents reported that exacerbations were "sometimes" or "frequently" fatal (Respir. Med. 2007;101:2011-6).

If these are not fatal, they often leave patients significantly worse than they were before, unlike exacerbations in other forms of lung disease, said Dr. Collard, who was the survey’s lead investigator.

Potential causes of acute worsening include infection, aspiration, myocardial infarction, pulmonary embolism, pneumothorax, and heart failure, as well as idiopathic causes. Acute worsening has not been studied in all ILDs, but it has been most closely studied in IPF. In Dr. Collard’s opinion, the best data on acute worsening in IPF come from a Korean cohort study of 461 patients with IPF who were followed longitudinally (Eur. Resp. J. 2011;37:356-63). The researchers divided patients into two groups: those with respiratory deterioration (defined as acute worsening with radiographic abnormalities) and those with acute exacerbation (defined as acute worsening in the absence of an identifiable etiology).

The researchers found that the 1-year incidence of respiratory deterioration was 23%, "which is higher than a lot of us have taken from clinical trials," Dr. Collard said. Of these cases, 55% were idiopathic, while the remainder had known causes that included infection and heart failure.

"These idiopathic acute worsenings, as defined in this study, are what we call acute exacerbation," Dr. Collard noted. "In IPF, acute exacerbation has a specific connotation compared with asthma or [chronic obstructive pulmonary disease]. It’s an idiopathic acute worsening."

The median survival among patients with acute exacerbation of IPF was 2.2 months from the onset of exacerbation. "This is a highly morbid and fatal condition," he said.

Dr. Collard led a panel of experts that established criteria for acute exacerbations of IPF (Am. J. Respir. Crit. Care Med. 2007;176:636-43). The criteria include previous or concurrent diagnosis of IPF, unexplained worsening or development of dyspnea over a period of 30 days or less, new bilateral ground glass and/or consolidation superimposed on a usual interstitial pneumonitis pattern on high-resolution CT, no microbiologic evidence of respiratory infection by endotracheal aspirate or bronchoalveolar lavage, and exclusion of other known causes of acute worsening.

According to the Korean IPF cohort study, significant risk factors for acute exacerbation include never having smoked tobacco and having a low forced vital capacity (FVC). "The higher your FVC, the lower your risk of acute exacerbation," Dr. Collard said. "That makes sense, [but] the protective effect of smoking is hard to explain."

He acknowledged that certain aspects of acute exacerbation remain elusive. "Does exacerbation actually represent an abrupt acceleration of the underlying disease process, or is it a manifestation of an occult secondary complication such as an infection that we’re missing because of the limitations of our clinical assessment?" he asked.

Researchers who conducted a test of gene expression profiling in this patient population found no differences in the global expression pattern between patients with stable IPF and those with acute exacerbation (Am. J. Respir. Crit. Care Med. 2009;180:167-75). "They did find evidence of enhanced alveolar epithelial cell activity," Dr. Collard said. "That was the main predominant pattern."

A study of biomarkers conducted by Dr. Collard and his associates yielded similar findings (Am. J. Physiol. Lung Cell Mol. Physiol. 2010;299:L3-7).

Dr. Collard hypothesized that acute exacerbation of IPF represents a primary acceleration of IPF in the setting of acute lung stress. "This stress may be minor, at a level that would not cause clinical disease in a normal lung," he said. Potential sources of stress include infection, occult aspiration, interventions, and drugs.

Dr. Collard disclosed that he receives research funding from the National Institutes of Health, the University of California, Boehringer Ingelheim, and Genentech. He also receives consulting fees from Fibrogen, Gilead, InterMune, and Onyx.

Asthma continues to be one of the most common chronic conditions complicating pregnancy; approximately 8% of pregnant women in the United States report a current diagnosis. Asthmatic women are at increased risk of adverse birth outcomes and perinatal complications, including spontaneous abortion, preterm delivery, reduced birth weight, preeclampsia, and in selected studies, congenital anomalies. In some cases, these increased risks have been linked to specific medications (for example, oral corticosteroid use is linked with orofacial clefts). But much of the current evidence is also consistent with the interpretation that at least some of the excess risk can be attributed to the underlying severity/inadequate control of maternal asthma.

However, two recently published studies suggest that beta₂-agonists – mainstays of treatment and control of asthma symptoms – may be associated with increased risks of congenital anomalies.

The first, an analysis conducted with data from the National Birth Defects Prevention Study, focused specifically on orofacial clefts as the outcome and bronchodilators as the exposure. Using a case control design, researchers interviewd 2,711 mothers of infants with oral clefts and 6,482 mothers of infants with no malformations in 10 states between 1997 and 2005 about bronchodilator use for asthma during and just before pregnancy. The authors separately evaluated risks for cleft lip alone, cleft lip with cleft palate, and cleft palate alone, as each of these defect categories may have distinct etiologies. Almost 3% (247 women) reported exposure to any bronchodilator in the periconceptional period, with nearly 90% of those exposures limited to the widely used short-acting beta₂-agonist, albuterol.

Significantly increased risks were noted for any bronchodilator use (without an additional anti-inflammatory drug) and cleft lip alone (adjusted odds ratio, 1.77; 95% confidence interval, 1.08-2.88); however, with the addition of an anti-inflammatory drug (four cases), the odds were attenuated and no longer statistically significant. Limiting the analysis to only those reporting use of albuterol, the estimated risks for cleft lip alone (adjusted OR, 1.79; 95% CI, 1.07-2.99) and cleft palate alone (adjusted OR, 1.65; 95% CI, 1.06-2.58) were both significantly elevated. No increased risks were noted for use of any bronchodilator and cleft lip with cleft palate. If these findings represent a causal association, the estimated odds ratios would translate to less than one excess case each of cleft lip alone and cleft palate alone for every 1,000 women using albuterol in the first trimester (Hum. Reprod. 2011;26:3147-54).

Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, with possible unintended risks for both mother and baby.

As the authors pointed out, there was no mechanism in the study to adjust for the contribution of underlying disease severity/asthma symptom control in these mothers. However, the lack of an association between orofacial clefts and bronchodilators among those women who also used an anti-inflammatory drug suggests that perhaps women on polytherapy had more optimum treatment and therefore better control.

The second study used a retrospective cohort design drawing on administrative data collected between 1990 and 2002 in Quebec. The 13,117 pregnancies selected for the analysis were limited to those with a coded diagnosis of asthma and excluded women who received multiple prescriptions for oral corticosteroids in the year before pregnancy. The exposures evaluated were any prescription in the periconceptional period for a short-acting beta₂-agonist rescue medication (such as albuterol), and any prescription in the periconceptional period for a long-acting beta₂-agonist controller medication (such as salmeterol, available during the years of this study as a single active ingredient medication). In all, 17 categories of major congenital malformations were evaluated as outcomes, including orofacial clefts. More than 50% of pregnant women in the study filled a prescription for a short-acting drug in the first trimester, while only 1.3% received a prescription for one of the long-acting medications.

The authors found no significant associations with short-acting beta₂-agonists for any of the congenital defect categories. Cases of cleft lip and cleft palate were combined, and the odds ratio after considering adjustment factors, was 1.50 (95% CI, 0.72-3.14). However, the authors did report that first trimester prescription for long-acting beta₂-agonists was associated with significantly increased risks for major cardiac malformations (adjusted OR, 2.30; 95% CI, 1.11-5.10) based on seven infants exposed and "other or unspecified major malformations" (adjusted OR, 3.97; 95% CI, 1.29-12.20) based on three infants exposed (Birth Defects Res. Clin. Molec. Teratol. 2011;91:937-47).

In this study, the authors attempted to control for underlying disease severity using Canadian treatment guidelines as well as emergency room and other hospital admissions for asthma. However, no direct measure of disease severity or symptom control was collected, and unfortunately, the "lumping" of orofacial clefts (likely due to the small number of affected infants) makes comparison to the above-described study difficult. The findings with long-acting beta₂-agonists, as the authors point out, could be influenced by the higher rate of more severe and less well-controlled asthma among these women, the expected higher rate of preterm delivery with associated prematurity-related defects, and/or multiple testing/chance. Finally, it has been suggested that some asthmatic women will reduce or discontinue medication in the first trimester of pregnancy based on fear of fetal exposure, not on remission of symptoms. If in fact this is the case, prescriptions filled may not reflect true usage of the drug.

With respect to previously published studies, an increased risk for congenital anomalies in general or orofacial clefts in particular, has not been suggested for albuterol. There is a lack of published data on long-acting beta₂-agonists and pregnancy outcome. Thus, although neither of the two new studies reviewed above will likely change clinical practice, they both point out the need for further study of commonly-used asthma medications, and specifically, studies that incorporate direct measures of disease severity/symptom control. Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, which in turn may result in unintended risks for both mother and baby.

Dr. Chambers is associate professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said she had no relevant financial disclosures.

Asthma continues to be one of the most common chronic conditions complicating pregnancy; approximately 8% of pregnant women in the United States report a current diagnosis. Asthmatic women are at increased risk of adverse birth outcomes and perinatal complications, including spontaneous abortion, preterm delivery, reduced birth weight, preeclampsia, and in selected studies, congenital anomalies. In some cases, these increased risks have been linked to specific medications (for example, oral corticosteroid use is linked with orofacial clefts). But much of the current evidence is also consistent with the interpretation that at least some of the excess risk can be attributed to the underlying severity/inadequate control of maternal asthma.

However, two recently published studies suggest that beta₂-agonists – mainstays of treatment and control of asthma symptoms – may be associated with increased risks of congenital anomalies.

The first, an analysis conducted with data from the National Birth Defects Prevention Study, focused specifically on orofacial clefts as the outcome and bronchodilators as the exposure. Using a case control design, researchers interviewd 2,711 mothers of infants with oral clefts and 6,482 mothers of infants with no malformations in 10 states between 1997 and 2005 about bronchodilator use for asthma during and just before pregnancy. The authors separately evaluated risks for cleft lip alone, cleft lip with cleft palate, and cleft palate alone, as each of these defect categories may have distinct etiologies. Almost 3% (247 women) reported exposure to any bronchodilator in the periconceptional period, with nearly 90% of those exposures limited to the widely used short-acting beta₂-agonist, albuterol.

Significantly increased risks were noted for any bronchodilator use (without an additional anti-inflammatory drug) and cleft lip alone (adjusted odds ratio, 1.77; 95% confidence interval, 1.08-2.88); however, with the addition of an anti-inflammatory drug (four cases), the odds were attenuated and no longer statistically significant. Limiting the analysis to only those reporting use of albuterol, the estimated risks for cleft lip alone (adjusted OR, 1.79; 95% CI, 1.07-2.99) and cleft palate alone (adjusted OR, 1.65; 95% CI, 1.06-2.58) were both significantly elevated. No increased risks were noted for use of any bronchodilator and cleft lip with cleft palate. If these findings represent a causal association, the estimated odds ratios would translate to less than one excess case each of cleft lip alone and cleft palate alone for every 1,000 women using albuterol in the first trimester (Hum. Reprod. 2011;26:3147-54).

Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, with possible unintended risks for both mother and baby.

As the authors pointed out, there was no mechanism in the study to adjust for the contribution of underlying disease severity/asthma symptom control in these mothers. However, the lack of an association between orofacial clefts and bronchodilators among those women who also used an anti-inflammatory drug suggests that perhaps women on polytherapy had more optimum treatment and therefore better control.

The second study used a retrospective cohort design drawing on administrative data collected between 1990 and 2002 in Quebec. The 13,117 pregnancies selected for the analysis were limited to those with a coded diagnosis of asthma and excluded women who received multiple prescriptions for oral corticosteroids in the year before pregnancy. The exposures evaluated were any prescription in the periconceptional period for a short-acting beta₂-agonist rescue medication (such as albuterol), and any prescription in the periconceptional period for a long-acting beta₂-agonist controller medication (such as salmeterol, available during the years of this study as a single active ingredient medication). In all, 17 categories of major congenital malformations were evaluated as outcomes, including orofacial clefts. More than 50% of pregnant women in the study filled a prescription for a short-acting drug in the first trimester, while only 1.3% received a prescription for one of the long-acting medications.

The authors found no significant associations with short-acting beta₂-agonists for any of the congenital defect categories. Cases of cleft lip and cleft palate were combined, and the odds ratio after considering adjustment factors, was 1.50 (95% CI, 0.72-3.14). However, the authors did report that first trimester prescription for long-acting beta₂-agonists was associated with significantly increased risks for major cardiac malformations (adjusted OR, 2.30; 95% CI, 1.11-5.10) based on seven infants exposed and "other or unspecified major malformations" (adjusted OR, 3.97; 95% CI, 1.29-12.20) based on three infants exposed (Birth Defects Res. Clin. Molec. Teratol. 2011;91:937-47).

In this study, the authors attempted to control for underlying disease severity using Canadian treatment guidelines as well as emergency room and other hospital admissions for asthma. However, no direct measure of disease severity or symptom control was collected, and unfortunately, the "lumping" of orofacial clefts (likely due to the small number of affected infants) makes comparison to the above-described study difficult. The findings with long-acting beta₂-agonists, as the authors point out, could be influenced by the higher rate of more severe and less well-controlled asthma among these women, the expected higher rate of preterm delivery with associated prematurity-related defects, and/or multiple testing/chance. Finally, it has been suggested that some asthmatic women will reduce or discontinue medication in the first trimester of pregnancy based on fear of fetal exposure, not on remission of symptoms. If in fact this is the case, prescriptions filled may not reflect true usage of the drug.

With respect to previously published studies, an increased risk for congenital anomalies in general or orofacial clefts in particular, has not been suggested for albuterol. There is a lack of published data on long-acting beta₂-agonists and pregnancy outcome. Thus, although neither of the two new studies reviewed above will likely change clinical practice, they both point out the need for further study of commonly-used asthma medications, and specifically, studies that incorporate direct measures of disease severity/symptom control. Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, which in turn may result in unintended risks for both mother and baby.

Dr. Chambers is associate professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said she had no relevant financial disclosures.

Asthma continues to be one of the most common chronic conditions complicating pregnancy; approximately 8% of pregnant women in the United States report a current diagnosis. Asthmatic women are at increased risk of adverse birth outcomes and perinatal complications, including spontaneous abortion, preterm delivery, reduced birth weight, preeclampsia, and in selected studies, congenital anomalies. In some cases, these increased risks have been linked to specific medications (for example, oral corticosteroid use is linked with orofacial clefts). But much of the current evidence is also consistent with the interpretation that at least some of the excess risk can be attributed to the underlying severity/inadequate control of maternal asthma.

However, two recently published studies suggest that beta₂-agonists – mainstays of treatment and control of asthma symptoms – may be associated with increased risks of congenital anomalies.

The first, an analysis conducted with data from the National Birth Defects Prevention Study, focused specifically on orofacial clefts as the outcome and bronchodilators as the exposure. Using a case control design, researchers interviewd 2,711 mothers of infants with oral clefts and 6,482 mothers of infants with no malformations in 10 states between 1997 and 2005 about bronchodilator use for asthma during and just before pregnancy. The authors separately evaluated risks for cleft lip alone, cleft lip with cleft palate, and cleft palate alone, as each of these defect categories may have distinct etiologies. Almost 3% (247 women) reported exposure to any bronchodilator in the periconceptional period, with nearly 90% of those exposures limited to the widely used short-acting beta₂-agonist, albuterol.

Significantly increased risks were noted for any bronchodilator use (without an additional anti-inflammatory drug) and cleft lip alone (adjusted odds ratio, 1.77; 95% confidence interval, 1.08-2.88); however, with the addition of an anti-inflammatory drug (four cases), the odds were attenuated and no longer statistically significant. Limiting the analysis to only those reporting use of albuterol, the estimated risks for cleft lip alone (adjusted OR, 1.79; 95% CI, 1.07-2.99) and cleft palate alone (adjusted OR, 1.65; 95% CI, 1.06-2.58) were both significantly elevated. No increased risks were noted for use of any bronchodilator and cleft lip with cleft palate. If these findings represent a causal association, the estimated odds ratios would translate to less than one excess case each of cleft lip alone and cleft palate alone for every 1,000 women using albuterol in the first trimester (Hum. Reprod. 2011;26:3147-54).

Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, with possible unintended risks for both mother and baby.

As the authors pointed out, there was no mechanism in the study to adjust for the contribution of underlying disease severity/asthma symptom control in these mothers. However, the lack of an association between orofacial clefts and bronchodilators among those women who also used an anti-inflammatory drug suggests that perhaps women on polytherapy had more optimum treatment and therefore better control.

The second study used a retrospective cohort design drawing on administrative data collected between 1990 and 2002 in Quebec. The 13,117 pregnancies selected for the analysis were limited to those with a coded diagnosis of asthma and excluded women who received multiple prescriptions for oral corticosteroids in the year before pregnancy. The exposures evaluated were any prescription in the periconceptional period for a short-acting beta₂-agonist rescue medication (such as albuterol), and any prescription in the periconceptional period for a long-acting beta₂-agonist controller medication (such as salmeterol, available during the years of this study as a single active ingredient medication). In all, 17 categories of major congenital malformations were evaluated as outcomes, including orofacial clefts. More than 50% of pregnant women in the study filled a prescription for a short-acting drug in the first trimester, while only 1.3% received a prescription for one of the long-acting medications.

The authors found no significant associations with short-acting beta₂-agonists for any of the congenital defect categories. Cases of cleft lip and cleft palate were combined, and the odds ratio after considering adjustment factors, was 1.50 (95% CI, 0.72-3.14). However, the authors did report that first trimester prescription for long-acting beta₂-agonists was associated with significantly increased risks for major cardiac malformations (adjusted OR, 2.30; 95% CI, 1.11-5.10) based on seven infants exposed and "other or unspecified major malformations" (adjusted OR, 3.97; 95% CI, 1.29-12.20) based on three infants exposed (Birth Defects Res. Clin. Molec. Teratol. 2011;91:937-47).

In this study, the authors attempted to control for underlying disease severity using Canadian treatment guidelines as well as emergency room and other hospital admissions for asthma. However, no direct measure of disease severity or symptom control was collected, and unfortunately, the "lumping" of orofacial clefts (likely due to the small number of affected infants) makes comparison to the above-described study difficult. The findings with long-acting beta₂-agonists, as the authors point out, could be influenced by the higher rate of more severe and less well-controlled asthma among these women, the expected higher rate of preterm delivery with associated prematurity-related defects, and/or multiple testing/chance. Finally, it has been suggested that some asthmatic women will reduce or discontinue medication in the first trimester of pregnancy based on fear of fetal exposure, not on remission of symptoms. If in fact this is the case, prescriptions filled may not reflect true usage of the drug.

With respect to previously published studies, an increased risk for congenital anomalies in general or orofacial clefts in particular, has not been suggested for albuterol. There is a lack of published data on long-acting beta₂-agonists and pregnancy outcome. Thus, although neither of the two new studies reviewed above will likely change clinical practice, they both point out the need for further study of commonly-used asthma medications, and specifically, studies that incorporate direct measures of disease severity/symptom control. Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, which in turn may result in unintended risks for both mother and baby.

Dr. Chambers is associate professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said she had no relevant financial disclosures.

A low-dose sublingual formulation of zolpidem tartrate is the first agent to be approved to treat insomnia characterized by middle-of-the-night waking followed by difficulty returning to sleep, the Food and Drug Administration announced Nov. 23.

Zolpidem tartrate was first approved in the United States in 1992 as the higher-dose formulation known as Ambien.

"For people whose insomnia causes them to wake in the middle of the night with difficulty returning to sleep, this new medication offers a safer choice than taking a higher dose of zolpidem upon waking," said Dr. Robert Temple, deputy center director for clinical science in the FDA’s Center for Drug Evaluation and Research, in a statement. "With this lower dose there is less risk of a person having too much drug in the body upon waking, which can cause dangerous drowsiness and impair driving."

Intermezzo (Transcept Pharmaceuticals Inc.) should only be used when a person has at least 4 hours of bedtime remaining. It should not be taken if alcohol has been consumed or with any other sleep aid.

The recommended and maximum dose of Intermezzo is 1.75 mg for women and 3.5 mg for men, taken once per night. The recommended dose for women is lower because women clear zolpidem from the body at a lower rate than men.

Intermezzo was studied in two clinical trials involving more than 370 patients. In the studies, patients taking the drug fell back to sleep faster after awakening as compared to people taking a placebo. The most commonly reported adverse reactions in the clinical trials were headache, nausea, and fatigue.

Potential side effects include getting out of bed while not fully awake and undertaking activities that are not remembered. Reported and not remembered activities have included driving a car, making and eating food, having sex, talking on the phone, and sleepwalking. Risks of such activities increase with use of alcohol or sedating drugs.

Intermezzo is a federally controlled substance.

A low-dose sublingual formulation of zolpidem tartrate is the first agent to be approved to treat insomnia characterized by middle-of-the-night waking followed by difficulty returning to sleep, the Food and Drug Administration announced Nov. 23.

Zolpidem tartrate was first approved in the United States in 1992 as the higher-dose formulation known as Ambien.

"For people whose insomnia causes them to wake in the middle of the night with difficulty returning to sleep, this new medication offers a safer choice than taking a higher dose of zolpidem upon waking," said Dr. Robert Temple, deputy center director for clinical science in the FDA’s Center for Drug Evaluation and Research, in a statement. "With this lower dose there is less risk of a person having too much drug in the body upon waking, which can cause dangerous drowsiness and impair driving."

Intermezzo (Transcept Pharmaceuticals Inc.) should only be used when a person has at least 4 hours of bedtime remaining. It should not be taken if alcohol has been consumed or with any other sleep aid.

The recommended and maximum dose of Intermezzo is 1.75 mg for women and 3.5 mg for men, taken once per night. The recommended dose for women is lower because women clear zolpidem from the body at a lower rate than men.

Intermezzo was studied in two clinical trials involving more than 370 patients. In the studies, patients taking the drug fell back to sleep faster after awakening as compared to people taking a placebo. The most commonly reported adverse reactions in the clinical trials were headache, nausea, and fatigue.

Potential side effects include getting out of bed while not fully awake and undertaking activities that are not remembered. Reported and not remembered activities have included driving a car, making and eating food, having sex, talking on the phone, and sleepwalking. Risks of such activities increase with use of alcohol or sedating drugs.

Intermezzo is a federally controlled substance.

A low-dose sublingual formulation of zolpidem tartrate is the first agent to be approved to treat insomnia characterized by middle-of-the-night waking followed by difficulty returning to sleep, the Food and Drug Administration announced Nov. 23.

Zolpidem tartrate was first approved in the United States in 1992 as the higher-dose formulation known as Ambien.

"For people whose insomnia causes them to wake in the middle of the night with difficulty returning to sleep, this new medication offers a safer choice than taking a higher dose of zolpidem upon waking," said Dr. Robert Temple, deputy center director for clinical science in the FDA’s Center for Drug Evaluation and Research, in a statement. "With this lower dose there is less risk of a person having too much drug in the body upon waking, which can cause dangerous drowsiness and impair driving."

Intermezzo (Transcept Pharmaceuticals Inc.) should only be used when a person has at least 4 hours of bedtime remaining. It should not be taken if alcohol has been consumed or with any other sleep aid.

The recommended and maximum dose of Intermezzo is 1.75 mg for women and 3.5 mg for men, taken once per night. The recommended dose for women is lower because women clear zolpidem from the body at a lower rate than men.

Intermezzo was studied in two clinical trials involving more than 370 patients. In the studies, patients taking the drug fell back to sleep faster after awakening as compared to people taking a placebo. The most commonly reported adverse reactions in the clinical trials were headache, nausea, and fatigue.

Potential side effects include getting out of bed while not fully awake and undertaking activities that are not remembered. Reported and not remembered activities have included driving a car, making and eating food, having sex, talking on the phone, and sleepwalking. Risks of such activities increase with use of alcohol or sedating drugs.

Intermezzo is a federally controlled substance.

Talking about end-of-life planning might not be so simple. Data suggests that patients want to know more about their prognosis, but sometimes physicians aren't sure how to bring up the discussion. Four supportive oncology experts discuss the importance and challenges of end-of-life planning during the 7th annual Chicago Supportive Oncology Conference.

Talking about end-of-life planning might not be so simple. Data suggests that patients want to know more about their prognosis, but sometimes physicians aren't sure how to bring up the discussion. Four supportive oncology experts discuss the importance and challenges of end-of-life planning during the 7th annual Chicago Supportive Oncology Conference.

Talking about end-of-life planning might not be so simple. Data suggests that patients want to know more about their prognosis, but sometimes physicians aren't sure how to bring up the discussion. Four supportive oncology experts discuss the importance and challenges of end-of-life planning during the 7th annual Chicago Supportive Oncology Conference.

PHILADELPHIA – When it comes to environmental health hazards, children are canaries in the coal shaft.

That’s because children are not just scaled-down adults. "Children are a lot more vulnerable to environmental hazards than adults," Dr. Jerome A. Paulson said at a conference sponsored by the Mid-Atlantic Center for Children's Health and the Environment. Factors behind the increased vulnerability include their small mass for a given dose of food or water contamination, increased transdermal absorption due to thinner skin and increased surface-area-to-mass ratio, more hand-to-mouth activity, more time spent on the ground, higher relative minute ventilation, and a longer window of exposure due to their longer life expectancy compared with adults, said Dr. Paulson, a pediatrician at George Washington University and director of the Mid-Atlantic Center for Children’s Health and the Environment in Washington, D.C.

Children, like adults, face an ever-growing list of potential environmental hazards. Here are some of the newer additions to Dr. Paulson’s list of concerns:

• Organophosphates. This pesticide class that includes malathion has been implicated in causing adverse neurodevelopmental effects. A 2004 report linked infant exposure to decrements in memory, attention, motor tasks, and behavior (Environ. Health Perspect. 2004;112:46-51). A report last year linked detectable levels of organophosphates in children aged 8-15 years with an increased risk for attention-deficit/hyperactivity disorder (Pediatrics 2010;125:e1270-7).

• Pyrethrins. This pesticide class has grown more popular as health concerns cut sales of other pesticides. Since 2000, calls to poison control centers and visits to health facilities due to exposure to pyrethrins and the related pyrethroids steadily increased (J. Med. Toxicol. 2007;3:94-9). Pyrethrins are commonly accepted as safe for children, and are in head lice products, but their long-term neurologic effects have not been thoroughly evaluated.

• Bisphenol A (BPA). Until recently, BPA was widely used as a hardener agent in plastics, although originally it was developed as a synthetic estrogen. This led to concerns about its impact on endocrinologic function and reproduction, as well as effects on metabolism and neurodevelopment (Environ. Health Perspect. 2009;117:1945-52; Curr. Opin. Pediatr. 2011;23:233-9).

• Phthalates. This widely used plasticizer softens plastics, but also appears in a huge variety of other products including packaging, cosmetics, lotions, vinyl flooring, and fragrances. Classified as endocrine-disrupting chemicals, results from preliminary studies suggest possible effects on reproduction, a possible role as an allergen, and possible carcinogenic effects, but more study is needed (J. Med. Toxicol. 2006;2:126-35).

• Manganese. This metal in gasoline and industrial waste that can appear in air, water, and soil has been linked with impaired development in infants and toddlers and low IQ scores in children aged 11-13 years (Lancet 2006;368:2167-78).

• Arsenic. A classic heavy metal toxin that causes multi-organ system injury, it can cause neurotoxicity at chronic, low levels, producing impaired verbal IQ scores and memory (Neurotoxicology 2006;27:210-6).

• Global Climate Change. This was called by Dr. Paulson "the single most important environmental health threat to children today because it impacts every single child." It is a cause of air pollution, severe weather, vector-borne infectious diseases, floods, draughts, malnutrition, and so on.

Dr. Paulson said that he had no relevant financial disclosures.

PHILADELPHIA – When it comes to environmental health hazards, children are canaries in the coal shaft.

That’s because children are not just scaled-down adults. "Children are a lot more vulnerable to environmental hazards than adults," Dr. Jerome A. Paulson said at a conference sponsored by the Mid-Atlantic Center for Children's Health and the Environment. Factors behind the increased vulnerability include their small mass for a given dose of food or water contamination, increased transdermal absorption due to thinner skin and increased surface-area-to-mass ratio, more hand-to-mouth activity, more time spent on the ground, higher relative minute ventilation, and a longer window of exposure due to their longer life expectancy compared with adults, said Dr. Paulson, a pediatrician at George Washington University and director of the Mid-Atlantic Center for Children’s Health and the Environment in Washington, D.C.

Children, like adults, face an ever-growing list of potential environmental hazards. Here are some of the newer additions to Dr. Paulson’s list of concerns:

• Organophosphates. This pesticide class that includes malathion has been implicated in causing adverse neurodevelopmental effects. A 2004 report linked infant exposure to decrements in memory, attention, motor tasks, and behavior (Environ. Health Perspect. 2004;112:46-51). A report last year linked detectable levels of organophosphates in children aged 8-15 years with an increased risk for attention-deficit/hyperactivity disorder (Pediatrics 2010;125:e1270-7).

• Pyrethrins. This pesticide class has grown more popular as health concerns cut sales of other pesticides. Since 2000, calls to poison control centers and visits to health facilities due to exposure to pyrethrins and the related pyrethroids steadily increased (J. Med. Toxicol. 2007;3:94-9). Pyrethrins are commonly accepted as safe for children, and are in head lice products, but their long-term neurologic effects have not been thoroughly evaluated.

• Bisphenol A (BPA). Until recently, BPA was widely used as a hardener agent in plastics, although originally it was developed as a synthetic estrogen. This led to concerns about its impact on endocrinologic function and reproduction, as well as effects on metabolism and neurodevelopment (Environ. Health Perspect. 2009;117:1945-52; Curr. Opin. Pediatr. 2011;23:233-9).

• Phthalates. This widely used plasticizer softens plastics, but also appears in a huge variety of other products including packaging, cosmetics, lotions, vinyl flooring, and fragrances. Classified as endocrine-disrupting chemicals, results from preliminary studies suggest possible effects on reproduction, a possible role as an allergen, and possible carcinogenic effects, but more study is needed (J. Med. Toxicol. 2006;2:126-35).

• Manganese. This metal in gasoline and industrial waste that can appear in air, water, and soil has been linked with impaired development in infants and toddlers and low IQ scores in children aged 11-13 years (Lancet 2006;368:2167-78).

• Arsenic. A classic heavy metal toxin that causes multi-organ system injury, it can cause neurotoxicity at chronic, low levels, producing impaired verbal IQ scores and memory (Neurotoxicology 2006;27:210-6).

• Global Climate Change. This was called by Dr. Paulson "the single most important environmental health threat to children today because it impacts every single child." It is a cause of air pollution, severe weather, vector-borne infectious diseases, floods, draughts, malnutrition, and so on.

Dr. Paulson said that he had no relevant financial disclosures.

PHILADELPHIA – When it comes to environmental health hazards, children are canaries in the coal shaft.

That’s because children are not just scaled-down adults. "Children are a lot more vulnerable to environmental hazards than adults," Dr. Jerome A. Paulson said at a conference sponsored by the Mid-Atlantic Center for Children's Health and the Environment. Factors behind the increased vulnerability include their small mass for a given dose of food or water contamination, increased transdermal absorption due to thinner skin and increased surface-area-to-mass ratio, more hand-to-mouth activity, more time spent on the ground, higher relative minute ventilation, and a longer window of exposure due to their longer life expectancy compared with adults, said Dr. Paulson, a pediatrician at George Washington University and director of the Mid-Atlantic Center for Children’s Health and the Environment in Washington, D.C.

Children, like adults, face an ever-growing list of potential environmental hazards. Here are some of the newer additions to Dr. Paulson’s list of concerns:

• Organophosphates. This pesticide class that includes malathion has been implicated in causing adverse neurodevelopmental effects. A 2004 report linked infant exposure to decrements in memory, attention, motor tasks, and behavior (Environ. Health Perspect. 2004;112:46-51). A report last year linked detectable levels of organophosphates in children aged 8-15 years with an increased risk for attention-deficit/hyperactivity disorder (Pediatrics 2010;125:e1270-7).

• Pyrethrins. This pesticide class has grown more popular as health concerns cut sales of other pesticides. Since 2000, calls to poison control centers and visits to health facilities due to exposure to pyrethrins and the related pyrethroids steadily increased (J. Med. Toxicol. 2007;3:94-9). Pyrethrins are commonly accepted as safe for children, and are in head lice products, but their long-term neurologic effects have not been thoroughly evaluated.

• Bisphenol A (BPA). Until recently, BPA was widely used as a hardener agent in plastics, although originally it was developed as a synthetic estrogen. This led to concerns about its impact on endocrinologic function and reproduction, as well as effects on metabolism and neurodevelopment (Environ. Health Perspect. 2009;117:1945-52; Curr. Opin. Pediatr. 2011;23:233-9).

• Phthalates. This widely used plasticizer softens plastics, but also appears in a huge variety of other products including packaging, cosmetics, lotions, vinyl flooring, and fragrances. Classified as endocrine-disrupting chemicals, results from preliminary studies suggest possible effects on reproduction, a possible role as an allergen, and possible carcinogenic effects, but more study is needed (J. Med. Toxicol. 2006;2:126-35).

• Manganese. This metal in gasoline and industrial waste that can appear in air, water, and soil has been linked with impaired development in infants and toddlers and low IQ scores in children aged 11-13 years (Lancet 2006;368:2167-78).

• Arsenic. A classic heavy metal toxin that causes multi-organ system injury, it can cause neurotoxicity at chronic, low levels, producing impaired verbal IQ scores and memory (Neurotoxicology 2006;27:210-6).

• Global Climate Change. This was called by Dr. Paulson "the single most important environmental health threat to children today because it impacts every single child." It is a cause of air pollution, severe weather, vector-borne infectious diseases, floods, draughts, malnutrition, and so on.

Dr. Paulson said that he had no relevant financial disclosures.

HONOLULU – Although large numbers of patients are surviving acute lung injury/adult respiratory distress syndrome, long-term impairments are common and "striking for their relationship to neuropsychiatric dysfunction," Dr. Jesse Hall said at the annual meeting of the American College of Chest Physicians.

"The pace of recovery is protracted and likely incomplete in the current paradigm of care," said Dr. Hall, professor of medicine, anesthesia, and critical care at the University of Chicago. "Interventions including those begun at the onset of critical illness will hopefully improve these outcomes."

According to the best epidemiologic study on the topic, an estimated 191,000 cases of acute lung injury (ALI) and 141,500 cases of adult respiratory distress syndrome (ARDS) occur each year in the United States, causing a combined 133,500 deaths annually (N. Engl. J. Med 2005;353:1685-93). Implementation of low-tidal-volume ventilation over the past decade has led to an improvement in survival among this patient population, Dr. Hall said, but "we are just beginning to understand through descriptive studies what the path is for these patients down the road. We really lack many prospective trials in that arena."

One study of 109 ARDS patients who were followed for 1 year found that most developed a restrictive lung lesion that improved in the first 6-12 months (N. Engl. J. Med 2003;348:683-93). "The most consistent pulmonary function test abnormality tends to be low diffusion capacity that often resolves over time," Dr. Hall said. Some of their general functional limitation correlates to their pulmonary dysfunction, "but much of it does not," he said. "In fact, it’s not what the patients report. They start to have a very low functional status 6, 12, and more months out, and they don’t ascribe it primarily to their lung dysfunction."

Residual areas of fibrosis are not unusual on follow-up CT scans of ALI/ARDS patients, and many of these patients develop airway abnormalities such as bronchiectasis associated with their lung injury, said Dr. Hall, who is also section chief of pulmonary and critical care medicine at the University of Chicago.

The 2003 study of 109 ARDS patients found that all subjects reported poor function due to loss of muscle bulk, proximal weakness, and fatigue. Some (12%) reported persistent pain at the chest tube site, 7% reported entrapment neuropathies, 7% had tracheotomy site problems, 5% had large joint enlargement/immobility from heterotopic ossification, and 4% had immobility in the form of contracted fingers or frozen shoulders. "It can be up to a year before patients regain their body weight after this episode," Dr. Hall said.

Neuromuscular sequelae may include myopathy, peripheral neuropathy, or deconditioning. "Any given patient can have any combination of those," he said. "Some of these disorders are reasonably strongly associated with some of our therapies. Most of our patients have a combination of peripheral neuropathies and myopathies that may by themselves be modest but are attended by extreme deconditioning. The neuromuscular sequelae of critical illness are variable in terms of recovery over months and years, and some patients seem to never fully recover."

The impact of neuropsychiatric sequelae can be significant. One study of 55 ARDS patients found that 100% had cognitive and affective impairments at hospital discharge, and 30% had generalized cognitive decline 1 year later (Am. J. Respir. Crit. Care Med. 1999;160:50-6). In the 2003 study, only 49% of the ARDS patients who had been employed were back to work at 1 year. "This is an astounding economic and financial consequence for the patient and the family," Dr. Hall commented. "Scores on the Short Form-36 were below normal in all eight domains at 3-, 6-, and 12-month follow-up from ICU discharge. There were improvements in most SF-36 categories, but almost none were back to normal."

Dr. Hall said that changes in the current health care system are needed to improve outcomes for ALI/ARDS patients. Currently, "it’s difficult for those in our discipline to figure out how to become a change agent, or help our patients acquire what they need to optimize their recovery," he explained. "It’s not likely, in fact, to be done by critical care doctors down the road."

One study from the United Kingdom sought to determine if giving patients a self-help rehabilitation manual would affect their general functional status "and therefore their psychiatric axes as well, and maybe even make them more functional," Dr. Hall said. For the study, patients in the control group received ward visits, three telephone calls at home, and clinic appointments at 8 weeks and 6 months, whereas patients in the intervention group received the same plus a 6-week self-help rehabilitation manual. At the end of 6 weeks, patients in the intervention group had significantly better physical function scores, compared with controls (Crit. Care Med. 2003;31:2456-61). Unfortunately, such benefits were not seen in another recent prospective trial.

In a recent trial conducted by a group of researchers that included Dr. Hall, 104 critical care patients who required ventilation were randomized to either early physical and occupational therapy during periods of daily interruption of sedation, or to daily interruption of sedation with therapy as ordered by the primary care team (Lancet 2009;373:1874-82). Compared with controls, patients who received early physical and occupational therapy had better return to independent functional status at hospital discharge (59% vs. 35%, respectively) and less ICU delirium (2 days vs. 4 days).

Dr. Hall concluded by noting that the brain and the neurologic and musculoskeletal systems "are likely the last to recover after ALI/ARDS, and may not recover fully to the status patients had before. We don’t know what matters most for long-term recovery. It’s reasonable to think that shortening ICU and mechanical ventilation time would be beneficial."

Dr. Hall disclosed that he receives honoraria from the American College of Chest Physicians and the American Thoracic Society.

HONOLULU – Although large numbers of patients are surviving acute lung injury/adult respiratory distress syndrome, long-term impairments are common and "striking for their relationship to neuropsychiatric dysfunction," Dr. Jesse Hall said at the annual meeting of the American College of Chest Physicians.

"The pace of recovery is protracted and likely incomplete in the current paradigm of care," said Dr. Hall, professor of medicine, anesthesia, and critical care at the University of Chicago. "Interventions including those begun at the onset of critical illness will hopefully improve these outcomes."

According to the best epidemiologic study on the topic, an estimated 191,000 cases of acute lung injury (ALI) and 141,500 cases of adult respiratory distress syndrome (ARDS) occur each year in the United States, causing a combined 133,500 deaths annually (N. Engl. J. Med 2005;353:1685-93). Implementation of low-tidal-volume ventilation over the past decade has led to an improvement in survival among this patient population, Dr. Hall said, but "we are just beginning to understand through descriptive studies what the path is for these patients down the road. We really lack many prospective trials in that arena."

One study of 109 ARDS patients who were followed for 1 year found that most developed a restrictive lung lesion that improved in the first 6-12 months (N. Engl. J. Med 2003;348:683-93). "The most consistent pulmonary function test abnormality tends to be low diffusion capacity that often resolves over time," Dr. Hall said. Some of their general functional limitation correlates to their pulmonary dysfunction, "but much of it does not," he said. "In fact, it’s not what the patients report. They start to have a very low functional status 6, 12, and more months out, and they don’t ascribe it primarily to their lung dysfunction."

Residual areas of fibrosis are not unusual on follow-up CT scans of ALI/ARDS patients, and many of these patients develop airway abnormalities such as bronchiectasis associated with their lung injury, said Dr. Hall, who is also section chief of pulmonary and critical care medicine at the University of Chicago.

The 2003 study of 109 ARDS patients found that all subjects reported poor function due to loss of muscle bulk, proximal weakness, and fatigue. Some (12%) reported persistent pain at the chest tube site, 7% reported entrapment neuropathies, 7% had tracheotomy site problems, 5% had large joint enlargement/immobility from heterotopic ossification, and 4% had immobility in the form of contracted fingers or frozen shoulders. "It can be up to a year before patients regain their body weight after this episode," Dr. Hall said.

Neuromuscular sequelae may include myopathy, peripheral neuropathy, or deconditioning. "Any given patient can have any combination of those," he said. "Some of these disorders are reasonably strongly associated with some of our therapies. Most of our patients have a combination of peripheral neuropathies and myopathies that may by themselves be modest but are attended by extreme deconditioning. The neuromuscular sequelae of critical illness are variable in terms of recovery over months and years, and some patients seem to never fully recover."

The impact of neuropsychiatric sequelae can be significant. One study of 55 ARDS patients found that 100% had cognitive and affective impairments at hospital discharge, and 30% had generalized cognitive decline 1 year later (Am. J. Respir. Crit. Care Med. 1999;160:50-6). In the 2003 study, only 49% of the ARDS patients who had been employed were back to work at 1 year. "This is an astounding economic and financial consequence for the patient and the family," Dr. Hall commented. "Scores on the Short Form-36 were below normal in all eight domains at 3-, 6-, and 12-month follow-up from ICU discharge. There were improvements in most SF-36 categories, but almost none were back to normal."

Dr. Hall said that changes in the current health care system are needed to improve outcomes for ALI/ARDS patients. Currently, "it’s difficult for those in our discipline to figure out how to become a change agent, or help our patients acquire what they need to optimize their recovery," he explained. "It’s not likely, in fact, to be done by critical care doctors down the road."

One study from the United Kingdom sought to determine if giving patients a self-help rehabilitation manual would affect their general functional status "and therefore their psychiatric axes as well, and maybe even make them more functional," Dr. Hall said. For the study, patients in the control group received ward visits, three telephone calls at home, and clinic appointments at 8 weeks and 6 months, whereas patients in the intervention group received the same plus a 6-week self-help rehabilitation manual. At the end of 6 weeks, patients in the intervention group had significantly better physical function scores, compared with controls (Crit. Care Med. 2003;31:2456-61). Unfortunately, such benefits were not seen in another recent prospective trial.

In a recent trial conducted by a group of researchers that included Dr. Hall, 104 critical care patients who required ventilation were randomized to either early physical and occupational therapy during periods of daily interruption of sedation, or to daily interruption of sedation with therapy as ordered by the primary care team (Lancet 2009;373:1874-82). Compared with controls, patients who received early physical and occupational therapy had better return to independent functional status at hospital discharge (59% vs. 35%, respectively) and less ICU delirium (2 days vs. 4 days).

Dr. Hall concluded by noting that the brain and the neurologic and musculoskeletal systems "are likely the last to recover after ALI/ARDS, and may not recover fully to the status patients had before. We don’t know what matters most for long-term recovery. It’s reasonable to think that shortening ICU and mechanical ventilation time would be beneficial."

Dr. Hall disclosed that he receives honoraria from the American College of Chest Physicians and the American Thoracic Society.

HONOLULU – Although large numbers of patients are surviving acute lung injury/adult respiratory distress syndrome, long-term impairments are common and "striking for their relationship to neuropsychiatric dysfunction," Dr. Jesse Hall said at the annual meeting of the American College of Chest Physicians.

"The pace of recovery is protracted and likely incomplete in the current paradigm of care," said Dr. Hall, professor of medicine, anesthesia, and critical care at the University of Chicago. "Interventions including those begun at the onset of critical illness will hopefully improve these outcomes."

According to the best epidemiologic study on the topic, an estimated 191,000 cases of acute lung injury (ALI) and 141,500 cases of adult respiratory distress syndrome (ARDS) occur each year in the United States, causing a combined 133,500 deaths annually (N. Engl. J. Med 2005;353:1685-93). Implementation of low-tidal-volume ventilation over the past decade has led to an improvement in survival among this patient population, Dr. Hall said, but "we are just beginning to understand through descriptive studies what the path is for these patients down the road. We really lack many prospective trials in that arena."

One study of 109 ARDS patients who were followed for 1 year found that most developed a restrictive lung lesion that improved in the first 6-12 months (N. Engl. J. Med 2003;348:683-93). "The most consistent pulmonary function test abnormality tends to be low diffusion capacity that often resolves over time," Dr. Hall said. Some of their general functional limitation correlates to their pulmonary dysfunction, "but much of it does not," he said. "In fact, it’s not what the patients report. They start to have a very low functional status 6, 12, and more months out, and they don’t ascribe it primarily to their lung dysfunction."

Residual areas of fibrosis are not unusual on follow-up CT scans of ALI/ARDS patients, and many of these patients develop airway abnormalities such as bronchiectasis associated with their lung injury, said Dr. Hall, who is also section chief of pulmonary and critical care medicine at the University of Chicago.

The 2003 study of 109 ARDS patients found that all subjects reported poor function due to loss of muscle bulk, proximal weakness, and fatigue. Some (12%) reported persistent pain at the chest tube site, 7% reported entrapment neuropathies, 7% had tracheotomy site problems, 5% had large joint enlargement/immobility from heterotopic ossification, and 4% had immobility in the form of contracted fingers or frozen shoulders. "It can be up to a year before patients regain their body weight after this episode," Dr. Hall said.

Neuromuscular sequelae may include myopathy, peripheral neuropathy, or deconditioning. "Any given patient can have any combination of those," he said. "Some of these disorders are reasonably strongly associated with some of our therapies. Most of our patients have a combination of peripheral neuropathies and myopathies that may by themselves be modest but are attended by extreme deconditioning. The neuromuscular sequelae of critical illness are variable in terms of recovery over months and years, and some patients seem to never fully recover."

The impact of neuropsychiatric sequelae can be significant. One study of 55 ARDS patients found that 100% had cognitive and affective impairments at hospital discharge, and 30% had generalized cognitive decline 1 year later (Am. J. Respir. Crit. Care Med. 1999;160:50-6). In the 2003 study, only 49% of the ARDS patients who had been employed were back to work at 1 year. "This is an astounding economic and financial consequence for the patient and the family," Dr. Hall commented. "Scores on the Short Form-36 were below normal in all eight domains at 3-, 6-, and 12-month follow-up from ICU discharge. There were improvements in most SF-36 categories, but almost none were back to normal."

Dr. Hall said that changes in the current health care system are needed to improve outcomes for ALI/ARDS patients. Currently, "it’s difficult for those in our discipline to figure out how to become a change agent, or help our patients acquire what they need to optimize their recovery," he explained. "It’s not likely, in fact, to be done by critical care doctors down the road."

One study from the United Kingdom sought to determine if giving patients a self-help rehabilitation manual would affect their general functional status "and therefore their psychiatric axes as well, and maybe even make them more functional," Dr. Hall said. For the study, patients in the control group received ward visits, three telephone calls at home, and clinic appointments at 8 weeks and 6 months, whereas patients in the intervention group received the same plus a 6-week self-help rehabilitation manual. At the end of 6 weeks, patients in the intervention group had significantly better physical function scores, compared with controls (Crit. Care Med. 2003;31:2456-61). Unfortunately, such benefits were not seen in another recent prospective trial.

In a recent trial conducted by a group of researchers that included Dr. Hall, 104 critical care patients who required ventilation were randomized to either early physical and occupational therapy during periods of daily interruption of sedation, or to daily interruption of sedation with therapy as ordered by the primary care team (Lancet 2009;373:1874-82). Compared with controls, patients who received early physical and occupational therapy had better return to independent functional status at hospital discharge (59% vs. 35%, respectively) and less ICU delirium (2 days vs. 4 days).

Dr. Hall concluded by noting that the brain and the neurologic and musculoskeletal systems "are likely the last to recover after ALI/ARDS, and may not recover fully to the status patients had before. We don’t know what matters most for long-term recovery. It’s reasonable to think that shortening ICU and mechanical ventilation time would be beneficial."

Dr. Hall disclosed that he receives honoraria from the American College of Chest Physicians and the American Thoracic Society.

HONOLULU – Having a higher body mass index is not significantly associated with hospital mortality among patients admitted to the surgical ICU.

While similar findings have been reported in medical ICUs, this is believed to be the largest study to investigate the relationship between BMI and mortality exclusively in a surgical ICU, Dr. Adam Khader said in an interview during a poster session at the annual meeting of the American College of Chest Physicians.

Dr. Khader, a resident in the department of surgery at Hofstra North Shore–Long Island Jewish Medical Center, Manhasset, N.Y., and his associates evaluated the records of 1,860 patients admitted to the medical center’s surgical ICU. Patients younger than age 18 years and those who did not undergo surgery were excluded from the analysis. The researchers used area under the receiver operating characteristic curves to assess the effect of BMI on mortality and categorized patients as underweight (BMI less than 20 kg/m²), normal weight (20-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), severely obese (35-50 kg/m²), and super obese (greater than 50 kg/m²).

Overall 30-day hospital mortality was 10%. Hospital mortality was 15% for underweight patients, 11% for normal weight patients, 8% for overweight patients, 9% for obese patients, 13% for severely obese patients, and 22% for super obese patients. Area under the receiver operating characteristic curve analysis yielded no significant association between BMI and mortality, even after stratification of patients by elective vs. emergent surgery, and patients younger vs. older than age 75 years.

Dr. Khader and his associates observed a trend toward increased mortality for patients in the underweight, obese, and severely obese categories of BMI, "but nothing statistically significant," he said. "Still, there was a large number of patients [in this study]. You can’t really ignore the numbers."

Dr. Khader said that he had no relevant financial conflicts to disclose.

HONOLULU – Having a higher body mass index is not significantly associated with hospital mortality among patients admitted to the surgical ICU.

While similar findings have been reported in medical ICUs, this is believed to be the largest study to investigate the relationship between BMI and mortality exclusively in a surgical ICU, Dr. Adam Khader said in an interview during a poster session at the annual meeting of the American College of Chest Physicians.

Dr. Khader, a resident in the department of surgery at Hofstra North Shore–Long Island Jewish Medical Center, Manhasset, N.Y., and his associates evaluated the records of 1,860 patients admitted to the medical center’s surgical ICU. Patients younger than age 18 years and those who did not undergo surgery were excluded from the analysis. The researchers used area under the receiver operating characteristic curves to assess the effect of BMI on mortality and categorized patients as underweight (BMI less than 20 kg/m²), normal weight (20-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), severely obese (35-50 kg/m²), and super obese (greater than 50 kg/m²).

Overall 30-day hospital mortality was 10%. Hospital mortality was 15% for underweight patients, 11% for normal weight patients, 8% for overweight patients, 9% for obese patients, 13% for severely obese patients, and 22% for super obese patients. Area under the receiver operating characteristic curve analysis yielded no significant association between BMI and mortality, even after stratification of patients by elective vs. emergent surgery, and patients younger vs. older than age 75 years.

Dr. Khader and his associates observed a trend toward increased mortality for patients in the underweight, obese, and severely obese categories of BMI, "but nothing statistically significant," he said. "Still, there was a large number of patients [in this study]. You can’t really ignore the numbers."

Dr. Khader said that he had no relevant financial conflicts to disclose.

HONOLULU – Having a higher body mass index is not significantly associated with hospital mortality among patients admitted to the surgical ICU.

While similar findings have been reported in medical ICUs, this is believed to be the largest study to investigate the relationship between BMI and mortality exclusively in a surgical ICU, Dr. Adam Khader said in an interview during a poster session at the annual meeting of the American College of Chest Physicians.

Dr. Khader, a resident in the department of surgery at Hofstra North Shore–Long Island Jewish Medical Center, Manhasset, N.Y., and his associates evaluated the records of 1,860 patients admitted to the medical center’s surgical ICU. Patients younger than age 18 years and those who did not undergo surgery were excluded from the analysis. The researchers used area under the receiver operating characteristic curves to assess the effect of BMI on mortality and categorized patients as underweight (BMI less than 20 kg/m²), normal weight (20-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), severely obese (35-50 kg/m²), and super obese (greater than 50 kg/m²).

Overall 30-day hospital mortality was 10%. Hospital mortality was 15% for underweight patients, 11% for normal weight patients, 8% for overweight patients, 9% for obese patients, 13% for severely obese patients, and 22% for super obese patients. Area under the receiver operating characteristic curve analysis yielded no significant association between BMI and mortality, even after stratification of patients by elective vs. emergent surgery, and patients younger vs. older than age 75 years.

Dr. Khader and his associates observed a trend toward increased mortality for patients in the underweight, obese, and severely obese categories of BMI, "but nothing statistically significant," he said. "Still, there was a large number of patients [in this study]. You can’t really ignore the numbers."

Dr. Khader said that he had no relevant financial conflicts to disclose.

HONOLULU – Not long ago, patients older than 65 years were rarely considered candidates for lung transplantation. But that’s not quite true anymore.

Being elderly is still a relative contraindication, but according to data from the International Society for Heart and Lung Transplantation, an increasing proportion of people older than age 65 are receiving lung transplants, from about 2% in 1995-1999 to about 6% between 2000 and June of 2010.

Instead of age and the length of time spent on the list waiting for a transplant, candidacy for the procedure is now based on whether patients’ advanced respiratory disease has progressed despite medical therapy, and whether they have a 50% or less chance of survival in the next 2-3 years, Dr. Luis F. Angel explained at the annual meeting of the American College of Chest Physicians.

"Potential candidates must be capable of comprehending the procedure, undergoing the selection process, and waiting the time necessary on the waiting list," said Dr. Angel, director of lung transplantation for the University of Texas Health Science Center at San Antonio.

In a review of the latest criteria, he explained that patients "must also be free of significant medical comorbidities and be sufficiently fit to handle this major surgical procedure and multiple medications post procedure."

The list of absolute contraindications for lung transplantation is lengthy, and includes recent malignancy (other than nonmelanoma skin cancer); infection with HIV; infection with hepatitis B or C with histologic evidence of cirrhosis; active cigarette smoking or substance abuse; severe and untreated psychiatric illness; documented noncompliance with medical care; and absence of a reliable social network.

Relative contraindications, Dr. Angel said, include the clinical state at the moment of notification or referral, such as the presence of hemodynamic instability, excessive physical deterioration, or severe muscle atrophy that impedes performing outpatient rehabilitation. Also taken into account is the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) support.

"Colonization by multiresistant or panresistant bacteria, fungus, or mycobacteria is another contraindication," Dr. Angel said, "as are other medical conditions such as coronary artery disease, liver and renal disease, gastroesophageal reflux, or symptomatic osteoporosis, and having a body mass index higher than 30 kg/m²."

Regarding the following specific indication for transplantation, the success rates vary according to the condition:

• COPD/emphysema. In a select group of patients with COPD/emphysema, transplantation provides both survival and quality of life benefits.

Referral criteria include a BODE index of 7-10 points, or at least one of the following: a history of hospitalization for exacerbation associated with acute hypercapnia; pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy; and an FEV₁ (forced expiratory volume in 1 second) of less than 20% and either a DLCO (diffusing capacity of the lungs for carbon monoxide) finding of less than 20% or homogenous distribution of emphysema.

• Pulmonary fibrosis. "The natural history of the disease is more predictable, and there are major limitations in effective therapy for this diagnosis," said Dr. Angel of the department of pulmonary and critical care medicine at the university.

Referral criteria, he said, include histologic or radiographic evidence of interstitial pneumonia, and any of the following: a DLCO of less than 39% predicted; a 10% or greater decrement in forced vital capacity during 6 months of follow-up; a decrease in pulse oximetry less than 88% during a 6-minute walk test; honeycombing on high-resolution CT; or development of secondary pulmonary hypertension.

• Cystic fibrosis. Patients with this condition "can get the most significant benefit and prolonged survival with lung transplantation," Dr. Angel said. "Referrals are often delayed, as there is [a] high emotional aspect in the management of these patients and their families."

Referral criteria, he said, include a FEV₁ of less than 30% of predicted, or rapidly declining lung function if FEV₁ is greater than 30% of predicted, and/or any of the following: increasing oxygen requirements, hypercapnia, and pulmonary hypertension.

• Idiopathic PAH (pulmonary arterial hypertension). "This is one of the most difficult conditions [in which] to determine the right time for transplantation," Dr. Angel said. "Significant improvements with medical therapy and increased awareness of the disease have decreased the number of lung transplants for this indication."

Referral criteria, he said, include persistent New York Heart Association class III or IV on maximal medical therapy; low or declining 6-minute walk test findings; failing therapy with intravenous epoprostenol or equivalent; a cardiac index of less than 2 L/min per square meter, or a right atrial pressure exceeding 15 mm Hg.

Dr. Angel said that he had no relevant financial conflicts to disclose.

HONOLULU – Not long ago, patients older than 65 years were rarely considered candidates for lung transplantation. But that’s not quite true anymore.

Being elderly is still a relative contraindication, but according to data from the International Society for Heart and Lung Transplantation, an increasing proportion of people older than age 65 are receiving lung transplants, from about 2% in 1995-1999 to about 6% between 2000 and June of 2010.

Instead of age and the length of time spent on the list waiting for a transplant, candidacy for the procedure is now based on whether patients’ advanced respiratory disease has progressed despite medical therapy, and whether they have a 50% or less chance of survival in the next 2-3 years, Dr. Luis F. Angel explained at the annual meeting of the American College of Chest Physicians.

"Potential candidates must be capable of comprehending the procedure, undergoing the selection process, and waiting the time necessary on the waiting list," said Dr. Angel, director of lung transplantation for the University of Texas Health Science Center at San Antonio.

In a review of the latest criteria, he explained that patients "must also be free of significant medical comorbidities and be sufficiently fit to handle this major surgical procedure and multiple medications post procedure."

The list of absolute contraindications for lung transplantation is lengthy, and includes recent malignancy (other than nonmelanoma skin cancer); infection with HIV; infection with hepatitis B or C with histologic evidence of cirrhosis; active cigarette smoking or substance abuse; severe and untreated psychiatric illness; documented noncompliance with medical care; and absence of a reliable social network.

Relative contraindications, Dr. Angel said, include the clinical state at the moment of notification or referral, such as the presence of hemodynamic instability, excessive physical deterioration, or severe muscle atrophy that impedes performing outpatient rehabilitation. Also taken into account is the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) support.

"Colonization by multiresistant or panresistant bacteria, fungus, or mycobacteria is another contraindication," Dr. Angel said, "as are other medical conditions such as coronary artery disease, liver and renal disease, gastroesophageal reflux, or symptomatic osteoporosis, and having a body mass index higher than 30 kg/m²."

Regarding the following specific indication for transplantation, the success rates vary according to the condition:

• COPD/emphysema. In a select group of patients with COPD/emphysema, transplantation provides both survival and quality of life benefits.

Referral criteria include a BODE index of 7-10 points, or at least one of the following: a history of hospitalization for exacerbation associated with acute hypercapnia; pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy; and an FEV₁ (forced expiratory volume in 1 second) of less than 20% and either a DLCO (diffusing capacity of the lungs for carbon monoxide) finding of less than 20% or homogenous distribution of emphysema.

• Pulmonary fibrosis. "The natural history of the disease is more predictable, and there are major limitations in effective therapy for this diagnosis," said Dr. Angel of the department of pulmonary and critical care medicine at the university.

Referral criteria, he said, include histologic or radiographic evidence of interstitial pneumonia, and any of the following: a DLCO of less than 39% predicted; a 10% or greater decrement in forced vital capacity during 6 months of follow-up; a decrease in pulse oximetry less than 88% during a 6-minute walk test; honeycombing on high-resolution CT; or development of secondary pulmonary hypertension.

• Cystic fibrosis. Patients with this condition "can get the most significant benefit and prolonged survival with lung transplantation," Dr. Angel said. "Referrals are often delayed, as there is [a] high emotional aspect in the management of these patients and their families."

Referral criteria, he said, include a FEV₁ of less than 30% of predicted, or rapidly declining lung function if FEV₁ is greater than 30% of predicted, and/or any of the following: increasing oxygen requirements, hypercapnia, and pulmonary hypertension.

• Idiopathic PAH (pulmonary arterial hypertension). "This is one of the most difficult conditions [in which] to determine the right time for transplantation," Dr. Angel said. "Significant improvements with medical therapy and increased awareness of the disease have decreased the number of lung transplants for this indication."

Referral criteria, he said, include persistent New York Heart Association class III or IV on maximal medical therapy; low or declining 6-minute walk test findings; failing therapy with intravenous epoprostenol or equivalent; a cardiac index of less than 2 L/min per square meter, or a right atrial pressure exceeding 15 mm Hg.

Dr. Angel said that he had no relevant financial conflicts to disclose.

HONOLULU – Not long ago, patients older than 65 years were rarely considered candidates for lung transplantation. But that’s not quite true anymore.

Being elderly is still a relative contraindication, but according to data from the International Society for Heart and Lung Transplantation, an increasing proportion of people older than age 65 are receiving lung transplants, from about 2% in 1995-1999 to about 6% between 2000 and June of 2010.

Instead of age and the length of time spent on the list waiting for a transplant, candidacy for the procedure is now based on whether patients’ advanced respiratory disease has progressed despite medical therapy, and whether they have a 50% or less chance of survival in the next 2-3 years, Dr. Luis F. Angel explained at the annual meeting of the American College of Chest Physicians.

"Potential candidates must be capable of comprehending the procedure, undergoing the selection process, and waiting the time necessary on the waiting list," said Dr. Angel, director of lung transplantation for the University of Texas Health Science Center at San Antonio.

In a review of the latest criteria, he explained that patients "must also be free of significant medical comorbidities and be sufficiently fit to handle this major surgical procedure and multiple medications post procedure."

The list of absolute contraindications for lung transplantation is lengthy, and includes recent malignancy (other than nonmelanoma skin cancer); infection with HIV; infection with hepatitis B or C with histologic evidence of cirrhosis; active cigarette smoking or substance abuse; severe and untreated psychiatric illness; documented noncompliance with medical care; and absence of a reliable social network.

Relative contraindications, Dr. Angel said, include the clinical state at the moment of notification or referral, such as the presence of hemodynamic instability, excessive physical deterioration, or severe muscle atrophy that impedes performing outpatient rehabilitation. Also taken into account is the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) support.

"Colonization by multiresistant or panresistant bacteria, fungus, or mycobacteria is another contraindication," Dr. Angel said, "as are other medical conditions such as coronary artery disease, liver and renal disease, gastroesophageal reflux, or symptomatic osteoporosis, and having a body mass index higher than 30 kg/m²."

Regarding the following specific indication for transplantation, the success rates vary according to the condition:

• COPD/emphysema. In a select group of patients with COPD/emphysema, transplantation provides both survival and quality of life benefits.

Referral criteria include a BODE index of 7-10 points, or at least one of the following: a history of hospitalization for exacerbation associated with acute hypercapnia; pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy; and an FEV₁ (forced expiratory volume in 1 second) of less than 20% and either a DLCO (diffusing capacity of the lungs for carbon monoxide) finding of less than 20% or homogenous distribution of emphysema.

• Pulmonary fibrosis. "The natural history of the disease is more predictable, and there are major limitations in effective therapy for this diagnosis," said Dr. Angel of the department of pulmonary and critical care medicine at the university.

Referral criteria, he said, include histologic or radiographic evidence of interstitial pneumonia, and any of the following: a DLCO of less than 39% predicted; a 10% or greater decrement in forced vital capacity during 6 months of follow-up; a decrease in pulse oximetry less than 88% during a 6-minute walk test; honeycombing on high-resolution CT; or development of secondary pulmonary hypertension.

• Cystic fibrosis. Patients with this condition "can get the most significant benefit and prolonged survival with lung transplantation," Dr. Angel said. "Referrals are often delayed, as there is [a] high emotional aspect in the management of these patients and their families."

Referral criteria, he said, include a FEV₁ of less than 30% of predicted, or rapidly declining lung function if FEV₁ is greater than 30% of predicted, and/or any of the following: increasing oxygen requirements, hypercapnia, and pulmonary hypertension.

• Idiopathic PAH (pulmonary arterial hypertension). "This is one of the most difficult conditions [in which] to determine the right time for transplantation," Dr. Angel said. "Significant improvements with medical therapy and increased awareness of the disease have decreased the number of lung transplants for this indication."

Referral criteria, he said, include persistent New York Heart Association class III or IV on maximal medical therapy; low or declining 6-minute walk test findings; failing therapy with intravenous epoprostenol or equivalent; a cardiac index of less than 2 L/min per square meter, or a right atrial pressure exceeding 15 mm Hg.

Dr. Angel said that he had no relevant financial conflicts to disclose.