Pulmonary Health Hub

The compound cytisine, an extract of acacia seeds that has been used in Eastern Europe for more than 40 years as an aid to smoking cessation, was found effective in the first placebo-controlled randomized trial of the agent that meets modern regulatory standards, according to a report in the Sept. 29 issue of the New England Journal of Medicine.

Cytisine is a partial agonist that binds with high affinity to a subtype of the nicotinic acetylcholine receptor, which is also the primary target of the smoking-cessation drug varenicline. It has been available across Eastern Europe under the brand name Tabex since 1964, said Robert West, Ph.D., of the Cancer Research U.K. Health Behavior Research Centre, department of epidemiology and public health, University College London, and his associates.

© milosluz/istockphoto.com

Because of its "unusual history of development," no preclinical studies, dosing studies, or large comparative trials have been reported to date. "We conducted a study to assess cytisine’s efficacy and safety in a context that could be replicated globally, with a relatively short treatment course (25 days) and minimal contact with health professionals," they noted.

Their aim was to determine whether the agent would be particularly beneficial for the millions of smokers who live in "countries in which the average household income is less than $200 per week and in which treatment of this kind is not paid for by insurance plans or national health care systems."

Unlike other pharmacotherapies for smoking cessation, cytisine is inexpensive; a full course of treatment costs the equivalent of $15 in Poland and $6 in Russia. This "may make it an attractive treatment option for smokers in low-income and middle-income countries," the researchers noted.

They performed a single-center, double-blind trial in which 740 subjects were randomly assigned to either active drug or placebo in equal numbers. "Behavioral support and the number of follow-up sessions were kept to a minimum to simulate, as much as possible, what might happen in a routine clinical situation" in low-income regions.

This included a baseline clinic visit where the drug was dispensed, telephone calls from staff on the target quit day (day 5) and 1 week later, a clinic visit 1 month after the target quit date, further follow-up calls, and a clinic visit for those who remained abstinent at 6 and 12 months following the conclusion of treatment.

The study participants were adults who smoked 10 or more cigarettes per day and were willing to try to stop smoking permanently. At baseline, all reported heavy smoking and showed high concentrations of carbon monoxide in exhaled breath, and all scored high on the Fagerström Test for Nicotine Dependence. Approximately half the study subjects were manual laborers, and more than 80% said they had tried to quit smoking previously.

The primary efficacy outcome was 12 months of sustained smoking abstinence after the end of treatment. This rate was 8.4% with cytisine, significantly better than the 2.4% rate with placebo.

"The net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4," Dr. West and his colleagues said (N. Engl. J. Med. 2011;365:1193-200).

This 3.4 relative difference in smoking cessation between cytisine and placebo "was higher than previous studies have shown for varenicline (2.3) and nicotine-replacement therapy (1.6). However, the absolute difference in the rate of abstinence between participants receiving cytisine and those receiving placebo in this trial (6 percentage points) was lower than that shown for varenicline and similar to that shown for nicotine-replacement therapy," they noted.

The rates of drug discontinuation or dose reduction were similar between subjects taking the active drug and those taking placebo. There were no serious adverse effects attributed to cytisine. The incidence of minor gastrointestinal adverse effects, chiefly stomach ache, dyspepsia, and nausea, was higher with cytisine than with placebo.

Using more intensive behavioral support along with cytisine may improve absolute quit rates. "Also, the treatment period was only 4 weeks, as compared with 8 weeks for nicotine-replacement therapy and 12 weeks for varenicline, and it is possible that efficacy could be improved by a longer regimen," the investigators added.

This study was supported by University College London, the U.K. National Prevention Research Initiative, Cancer Research U.K., and the U.K. National Institute for Health Research. Cytisine and matching placebo were provided at no cost by the manufacturer, Sopharma AD. Dr. West and his associates reported ties to Pfizer, McNeil, Celtic, Johnson & Johnson, and GlaxoSmithKline, and Dr. West holds a patent pending on a nicotine delivery device.

The compound cytisine, an extract of acacia seeds that has been used in Eastern Europe for more than 40 years as an aid to smoking cessation, was found effective in the first placebo-controlled randomized trial of the agent that meets modern regulatory standards, according to a report in the Sept. 29 issue of the New England Journal of Medicine.

Cytisine is a partial agonist that binds with high affinity to a subtype of the nicotinic acetylcholine receptor, which is also the primary target of the smoking-cessation drug varenicline. It has been available across Eastern Europe under the brand name Tabex since 1964, said Robert West, Ph.D., of the Cancer Research U.K. Health Behavior Research Centre, department of epidemiology and public health, University College London, and his associates.

© milosluz/istockphoto.com

Because of its "unusual history of development," no preclinical studies, dosing studies, or large comparative trials have been reported to date. "We conducted a study to assess cytisine’s efficacy and safety in a context that could be replicated globally, with a relatively short treatment course (25 days) and minimal contact with health professionals," they noted.

Their aim was to determine whether the agent would be particularly beneficial for the millions of smokers who live in "countries in which the average household income is less than $200 per week and in which treatment of this kind is not paid for by insurance plans or national health care systems."

Unlike other pharmacotherapies for smoking cessation, cytisine is inexpensive; a full course of treatment costs the equivalent of $15 in Poland and $6 in Russia. This "may make it an attractive treatment option for smokers in low-income and middle-income countries," the researchers noted.

They performed a single-center, double-blind trial in which 740 subjects were randomly assigned to either active drug or placebo in equal numbers. "Behavioral support and the number of follow-up sessions were kept to a minimum to simulate, as much as possible, what might happen in a routine clinical situation" in low-income regions.

This included a baseline clinic visit where the drug was dispensed, telephone calls from staff on the target quit day (day 5) and 1 week later, a clinic visit 1 month after the target quit date, further follow-up calls, and a clinic visit for those who remained abstinent at 6 and 12 months following the conclusion of treatment.

The study participants were adults who smoked 10 or more cigarettes per day and were willing to try to stop smoking permanently. At baseline, all reported heavy smoking and showed high concentrations of carbon monoxide in exhaled breath, and all scored high on the Fagerström Test for Nicotine Dependence. Approximately half the study subjects were manual laborers, and more than 80% said they had tried to quit smoking previously.

The primary efficacy outcome was 12 months of sustained smoking abstinence after the end of treatment. This rate was 8.4% with cytisine, significantly better than the 2.4% rate with placebo.

"The net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4," Dr. West and his colleagues said (N. Engl. J. Med. 2011;365:1193-200).

This 3.4 relative difference in smoking cessation between cytisine and placebo "was higher than previous studies have shown for varenicline (2.3) and nicotine-replacement therapy (1.6). However, the absolute difference in the rate of abstinence between participants receiving cytisine and those receiving placebo in this trial (6 percentage points) was lower than that shown for varenicline and similar to that shown for nicotine-replacement therapy," they noted.

The rates of drug discontinuation or dose reduction were similar between subjects taking the active drug and those taking placebo. There were no serious adverse effects attributed to cytisine. The incidence of minor gastrointestinal adverse effects, chiefly stomach ache, dyspepsia, and nausea, was higher with cytisine than with placebo.

Using more intensive behavioral support along with cytisine may improve absolute quit rates. "Also, the treatment period was only 4 weeks, as compared with 8 weeks for nicotine-replacement therapy and 12 weeks for varenicline, and it is possible that efficacy could be improved by a longer regimen," the investigators added.

This study was supported by University College London, the U.K. National Prevention Research Initiative, Cancer Research U.K., and the U.K. National Institute for Health Research. Cytisine and matching placebo were provided at no cost by the manufacturer, Sopharma AD. Dr. West and his associates reported ties to Pfizer, McNeil, Celtic, Johnson & Johnson, and GlaxoSmithKline, and Dr. West holds a patent pending on a nicotine delivery device.

The compound cytisine, an extract of acacia seeds that has been used in Eastern Europe for more than 40 years as an aid to smoking cessation, was found effective in the first placebo-controlled randomized trial of the agent that meets modern regulatory standards, according to a report in the Sept. 29 issue of the New England Journal of Medicine.

Cytisine is a partial agonist that binds with high affinity to a subtype of the nicotinic acetylcholine receptor, which is also the primary target of the smoking-cessation drug varenicline. It has been available across Eastern Europe under the brand name Tabex since 1964, said Robert West, Ph.D., of the Cancer Research U.K. Health Behavior Research Centre, department of epidemiology and public health, University College London, and his associates.

© milosluz/istockphoto.com

Because of its "unusual history of development," no preclinical studies, dosing studies, or large comparative trials have been reported to date. "We conducted a study to assess cytisine’s efficacy and safety in a context that could be replicated globally, with a relatively short treatment course (25 days) and minimal contact with health professionals," they noted.

Their aim was to determine whether the agent would be particularly beneficial for the millions of smokers who live in "countries in which the average household income is less than $200 per week and in which treatment of this kind is not paid for by insurance plans or national health care systems."

Unlike other pharmacotherapies for smoking cessation, cytisine is inexpensive; a full course of treatment costs the equivalent of $15 in Poland and $6 in Russia. This "may make it an attractive treatment option for smokers in low-income and middle-income countries," the researchers noted.

They performed a single-center, double-blind trial in which 740 subjects were randomly assigned to either active drug or placebo in equal numbers. "Behavioral support and the number of follow-up sessions were kept to a minimum to simulate, as much as possible, what might happen in a routine clinical situation" in low-income regions.

This included a baseline clinic visit where the drug was dispensed, telephone calls from staff on the target quit day (day 5) and 1 week later, a clinic visit 1 month after the target quit date, further follow-up calls, and a clinic visit for those who remained abstinent at 6 and 12 months following the conclusion of treatment.

The study participants were adults who smoked 10 or more cigarettes per day and were willing to try to stop smoking permanently. At baseline, all reported heavy smoking and showed high concentrations of carbon monoxide in exhaled breath, and all scored high on the Fagerström Test for Nicotine Dependence. Approximately half the study subjects were manual laborers, and more than 80% said they had tried to quit smoking previously.

The primary efficacy outcome was 12 months of sustained smoking abstinence after the end of treatment. This rate was 8.4% with cytisine, significantly better than the 2.4% rate with placebo.

"The net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4," Dr. West and his colleagues said (N. Engl. J. Med. 2011;365:1193-200).

This 3.4 relative difference in smoking cessation between cytisine and placebo "was higher than previous studies have shown for varenicline (2.3) and nicotine-replacement therapy (1.6). However, the absolute difference in the rate of abstinence between participants receiving cytisine and those receiving placebo in this trial (6 percentage points) was lower than that shown for varenicline and similar to that shown for nicotine-replacement therapy," they noted.

The rates of drug discontinuation or dose reduction were similar between subjects taking the active drug and those taking placebo. There were no serious adverse effects attributed to cytisine. The incidence of minor gastrointestinal adverse effects, chiefly stomach ache, dyspepsia, and nausea, was higher with cytisine than with placebo.

Using more intensive behavioral support along with cytisine may improve absolute quit rates. "Also, the treatment period was only 4 weeks, as compared with 8 weeks for nicotine-replacement therapy and 12 weeks for varenicline, and it is possible that efficacy could be improved by a longer regimen," the investigators added.

This study was supported by University College London, the U.K. National Prevention Research Initiative, Cancer Research U.K., and the U.K. National Institute for Health Research. Cytisine and matching placebo were provided at no cost by the manufacturer, Sopharma AD. Dr. West and his associates reported ties to Pfizer, McNeil, Celtic, Johnson & Johnson, and GlaxoSmithKline, and Dr. West holds a patent pending on a nicotine delivery device.

CHICAGO – Payers are relying ever more on tying physician and hospital payments to quality measures, but what happens if the benchmarks they use vary among institutions or are flawed? Such may be the case with ventilator-associated pneumonia and large trauma centers, as a recent study shows VAP rates at such facilities exceed national benchmarks, which some say are inadequate for comparison.

Dr. Christopher P. Michetti of Inova Fairfax Hospital in Falls Church, Va., presented a retrospective study designed to determine VAP rates at major trauma centers and to lay groundwork for more accurate benchmarking that relies less on National Health Safety Network data, he said. He spoke at the annual meeting of the American Association for Surgery in Trauma. The study was performed through the AAST Multi-Institutional Trials Committee.

"Hospitals are under pressure to reduce their VAP rates, yet a direct association between VAP rates and quality of care or outcomes has not been demonstrated," he remarked.

"VAP rates ...are remarkably variable," Dr. Michetti said. "It is not appropriate to measure all trauma centers against a single benchmark, nor does an actual benchmark appear to exist at this point." Comparing VAP rates between different trauma centers is "like comparing apples and oranges," he said.

The study looked at VAP rates at 47 level I and II trauma centers for 2008 and 2009 with an average of 3,000 trauma evaluations a year. The average VAP rate for the study group was 17.2/1,000 ventilator days, compared with 8.1/1,000 for NHSN data. "In fact, the 90th-percentile rate for NHSN was still below the mean rate from our study," Dr. Michetti said. Across all 47 centers in the study, VAP rates ranged from a low of 1.8/1,000 ventilator days to a high of 57.6/1,000 ventilator days.

The case mix at the trauma centers did not auger well for lower VAP rates, as 88% of the cases were blunt trauma, Dr. Michetti noted. "VAP rates are generally higher for blunt-trauma patients, at about 17/1,000 ventilator days, compared with penetrating trauma at 11/1,000," he said.

Most other variables among the centers in the study – such as having a closed or open ICU, or using a bacteriologic vs. a clinical strategy to diagnose VAP – showed little impact on the pneumonia rates. VAP rates did not correlate with the size or level of trauma center, injury severity or type of ICU, he said.

Among the problems he noted with the NHSN data on VAP rates are the lack of source hospital identification, population risk, or injury severity stratification. "In addition, the NHSN rates are substantially lower than other published rates among trauma patients," he said.

However, the investigators did isolate a few variables that may influence VAP rates: Among centers where the trauma service alone made the diagnosis, the average VAP rate was 27.5/1,000 ventilator days. When the infection control, quality, or epidemiology department made the call, the average VAP rate was 11.9/1,000 days. Centers that excluded patients also had rates about 30% lower than those that did not. This variability raises questions about using VAP as a quality measure, Dr. Michetti said. "Before we take that leap, diagnostic and reporting standards are necessary."

The heightened attention on VAP as a quality measure for critical care is having other implications, he said. "As pressure to reduce VAP rates grows, an increasing number of patients are being labeled as having ventilator-associated tracheobronchitis or excluded for reasons such as aspiration," he said.

Discussant Dr. Karen J. Brasel of the Medical College of Wisconsin in, Milwaukee, acknowledged the need for the study, but raised the question: "Are the benchmarks the problem, or are we the problem?"

"I think the answer is yes, both," Dr. Michetti said. "I’m not sure that an adequate benchmark exists probably because no representative sample of trauma centers has been done to set that benchmark." He noted that the CDC’s Healthcare Infection Control Practices Advisory Committee does not recommend reporting of VAP, which argues against using that as a benchmark. Meanwhile, across individual centers no reporting standards exist, "so centers can’t agree on what is VAP," Dr. Michetti said.

Dr. Michetti had no disclosures, and the study received no outside funding.

CHICAGO – Payers are relying ever more on tying physician and hospital payments to quality measures, but what happens if the benchmarks they use vary among institutions or are flawed? Such may be the case with ventilator-associated pneumonia and large trauma centers, as a recent study shows VAP rates at such facilities exceed national benchmarks, which some say are inadequate for comparison.

Dr. Christopher P. Michetti of Inova Fairfax Hospital in Falls Church, Va., presented a retrospective study designed to determine VAP rates at major trauma centers and to lay groundwork for more accurate benchmarking that relies less on National Health Safety Network data, he said. He spoke at the annual meeting of the American Association for Surgery in Trauma. The study was performed through the AAST Multi-Institutional Trials Committee.

"Hospitals are under pressure to reduce their VAP rates, yet a direct association between VAP rates and quality of care or outcomes has not been demonstrated," he remarked.

"VAP rates ...are remarkably variable," Dr. Michetti said. "It is not appropriate to measure all trauma centers against a single benchmark, nor does an actual benchmark appear to exist at this point." Comparing VAP rates between different trauma centers is "like comparing apples and oranges," he said.

The study looked at VAP rates at 47 level I and II trauma centers for 2008 and 2009 with an average of 3,000 trauma evaluations a year. The average VAP rate for the study group was 17.2/1,000 ventilator days, compared with 8.1/1,000 for NHSN data. "In fact, the 90th-percentile rate for NHSN was still below the mean rate from our study," Dr. Michetti said. Across all 47 centers in the study, VAP rates ranged from a low of 1.8/1,000 ventilator days to a high of 57.6/1,000 ventilator days.

The case mix at the trauma centers did not auger well for lower VAP rates, as 88% of the cases were blunt trauma, Dr. Michetti noted. "VAP rates are generally higher for blunt-trauma patients, at about 17/1,000 ventilator days, compared with penetrating trauma at 11/1,000," he said.

Most other variables among the centers in the study – such as having a closed or open ICU, or using a bacteriologic vs. a clinical strategy to diagnose VAP – showed little impact on the pneumonia rates. VAP rates did not correlate with the size or level of trauma center, injury severity or type of ICU, he said.

Among the problems he noted with the NHSN data on VAP rates are the lack of source hospital identification, population risk, or injury severity stratification. "In addition, the NHSN rates are substantially lower than other published rates among trauma patients," he said.

However, the investigators did isolate a few variables that may influence VAP rates: Among centers where the trauma service alone made the diagnosis, the average VAP rate was 27.5/1,000 ventilator days. When the infection control, quality, or epidemiology department made the call, the average VAP rate was 11.9/1,000 days. Centers that excluded patients also had rates about 30% lower than those that did not. This variability raises questions about using VAP as a quality measure, Dr. Michetti said. "Before we take that leap, diagnostic and reporting standards are necessary."

The heightened attention on VAP as a quality measure for critical care is having other implications, he said. "As pressure to reduce VAP rates grows, an increasing number of patients are being labeled as having ventilator-associated tracheobronchitis or excluded for reasons such as aspiration," he said.

Discussant Dr. Karen J. Brasel of the Medical College of Wisconsin in, Milwaukee, acknowledged the need for the study, but raised the question: "Are the benchmarks the problem, or are we the problem?"

"I think the answer is yes, both," Dr. Michetti said. "I’m not sure that an adequate benchmark exists probably because no representative sample of trauma centers has been done to set that benchmark." He noted that the CDC’s Healthcare Infection Control Practices Advisory Committee does not recommend reporting of VAP, which argues against using that as a benchmark. Meanwhile, across individual centers no reporting standards exist, "so centers can’t agree on what is VAP," Dr. Michetti said.

Dr. Michetti had no disclosures, and the study received no outside funding.

CHICAGO – Payers are relying ever more on tying physician and hospital payments to quality measures, but what happens if the benchmarks they use vary among institutions or are flawed? Such may be the case with ventilator-associated pneumonia and large trauma centers, as a recent study shows VAP rates at such facilities exceed national benchmarks, which some say are inadequate for comparison.

Dr. Christopher P. Michetti of Inova Fairfax Hospital in Falls Church, Va., presented a retrospective study designed to determine VAP rates at major trauma centers and to lay groundwork for more accurate benchmarking that relies less on National Health Safety Network data, he said. He spoke at the annual meeting of the American Association for Surgery in Trauma. The study was performed through the AAST Multi-Institutional Trials Committee.

"Hospitals are under pressure to reduce their VAP rates, yet a direct association between VAP rates and quality of care or outcomes has not been demonstrated," he remarked.

"VAP rates ...are remarkably variable," Dr. Michetti said. "It is not appropriate to measure all trauma centers against a single benchmark, nor does an actual benchmark appear to exist at this point." Comparing VAP rates between different trauma centers is "like comparing apples and oranges," he said.

The study looked at VAP rates at 47 level I and II trauma centers for 2008 and 2009 with an average of 3,000 trauma evaluations a year. The average VAP rate for the study group was 17.2/1,000 ventilator days, compared with 8.1/1,000 for NHSN data. "In fact, the 90th-percentile rate for NHSN was still below the mean rate from our study," Dr. Michetti said. Across all 47 centers in the study, VAP rates ranged from a low of 1.8/1,000 ventilator days to a high of 57.6/1,000 ventilator days.

The case mix at the trauma centers did not auger well for lower VAP rates, as 88% of the cases were blunt trauma, Dr. Michetti noted. "VAP rates are generally higher for blunt-trauma patients, at about 17/1,000 ventilator days, compared with penetrating trauma at 11/1,000," he said.

Most other variables among the centers in the study – such as having a closed or open ICU, or using a bacteriologic vs. a clinical strategy to diagnose VAP – showed little impact on the pneumonia rates. VAP rates did not correlate with the size or level of trauma center, injury severity or type of ICU, he said.

Among the problems he noted with the NHSN data on VAP rates are the lack of source hospital identification, population risk, or injury severity stratification. "In addition, the NHSN rates are substantially lower than other published rates among trauma patients," he said.

However, the investigators did isolate a few variables that may influence VAP rates: Among centers where the trauma service alone made the diagnosis, the average VAP rate was 27.5/1,000 ventilator days. When the infection control, quality, or epidemiology department made the call, the average VAP rate was 11.9/1,000 days. Centers that excluded patients also had rates about 30% lower than those that did not. This variability raises questions about using VAP as a quality measure, Dr. Michetti said. "Before we take that leap, diagnostic and reporting standards are necessary."

The heightened attention on VAP as a quality measure for critical care is having other implications, he said. "As pressure to reduce VAP rates grows, an increasing number of patients are being labeled as having ventilator-associated tracheobronchitis or excluded for reasons such as aspiration," he said.

Discussant Dr. Karen J. Brasel of the Medical College of Wisconsin in, Milwaukee, acknowledged the need for the study, but raised the question: "Are the benchmarks the problem, or are we the problem?"

"I think the answer is yes, both," Dr. Michetti said. "I’m not sure that an adequate benchmark exists probably because no representative sample of trauma centers has been done to set that benchmark." He noted that the CDC’s Healthcare Infection Control Practices Advisory Committee does not recommend reporting of VAP, which argues against using that as a benchmark. Meanwhile, across individual centers no reporting standards exist, "so centers can’t agree on what is VAP," Dr. Michetti said.

Dr. Michetti had no disclosures, and the study received no outside funding.

The rate of change in forced expiratory volume in 1 second among patients with chronic obstructive pulmonary disease is highly variable, with the greatest rates of decline occurring among current smokers, patients with bronchodilator reversibility, and those with emphysema, according to an analysis of data from the ECLIPSE observational study reported online Sept. 26 in the New England Journal of Medicine.

Research in the 1970s established that patients with COPD experience an accelerated decline in FEV₁, yet few longitudinal studies have provided detailed data about this decline. Also, none have provided information about FEV₁ in specific subgroups of patients with COPD or according to levels of specific biomarkers.

Dr. Jørgen Vestbo of the University of Copenhagen and his colleagues analyzed data collected for the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, which included 2,163 patients aged 40-75 years who had a smoking history of 10 or more pack-years and 80% of the predicted value and ratio of FEV₁ to forced vital capacity (FVC) of 0.7 or less (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMoa1105482]).

Specifically, the researchers analyzed changes in FEV₁ after bronchodilator use at baseline, 3 months, 6 months, and then every 6 months for 3 years. They defined subgroups according to the presence of emphysema and chronic bronchitis, bronchodilator reversibility, and cardiovascular disease. They also obtained serum and plasma samples for the following biomarkers: C-reactive protein, interleukin-8, interleukin-6, fibrinogen, tumor necrosis factor–alpha, surfactant protein D, and Clara cell secretory protein 16 (CC-16).

The rate of FEV₁ was highly variable during the 3-year period, the results showed. Overall, there was a mean decline of 33 mL/year. More specifically, 38% of patients had a decline of more than 40 mL/year, 31% had a decline of 21-40 mL/year, 23% had changes ranging from a decline of 20 mL/year to an increase of 20 mL/year, and 8% had an increase of more than 20 mL/year.

The researchers also found an inverse relationship between the declines in FEV₁ and stage of disease, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Mean rates of decline were 35 mL/year in patients with moderate disease (GOLD stage 2), 33 mL/year in patients with severe disease (GOLD stage 3), and 25 mL/year in patients with very severe disease (GOLD stage 4).

Smoking status was most strongly associated with the rate of decline, with current smokers experiencing a decline of 21 mL/year more than former smokers. However, cumulative exposure did not affect future decline. "This finding points to smoking cessation as the most important tool in secondary and tertiary prevention for patients at all stages of COPD," the researchers said.

Among the subgroups studied, FEV₁ declined by 17 mL more per year in patients with bronchodilator reversibility at baseline, compared with those without reversibility. Also, FEV₁ declined by an additional 13 mL/year in patients with clinically significant emphysema versus those with little or no emphysema. The presence of cardiovascular disease had no effect on FEV₁.

Although several biomarkers were associated with FEV₁ at baseline, only CC-16 levels were significantly associated with the rate of change in FEV₁, with an additional decline of 4 mL/year for each decrease of 1 standard deviation in the level of CC-16. "This association was weak, and whether it is biologically meaningful has yet to be determined," Dr. Vestbo and his colleagues said. "Without confirmation, it does not seem appropriate to speculate on the potential significance of this finding."

The study findings call into question whether COPD is invariably progressive. "In more than half the patients in our study, the rate of decline in FEV₁ over a period of 3 years was no greater than that which has been observed in people without lung disease. This finding could indicate that COPD may ‘burn out’ or at least stabilize for periods of 3 years or more, which would be good news for patients and could influence a variety of management decisions that depend on prognosis."

A limitation of the study was that it included only patients with moderate, severe, or very severe COPD, and therefore could not identify factors associated with rates of decline in early-stage COPD. Also, the study was purely observational and did not include treatment. "Moreover, the diagnosis and management of COPD in the patients in our study were carried out at specialist centers, and our results may not extend beyond this patient population for a variety of reasons, including the clinically determined care they received," the researchers said.

In an editorial accompanying the report, Dr. Peter Burney said this longitudinal analysis "did not confirm the promise of the earlier cross-sectional analysis [Eur. Respir. J. 2008;31:869-73] by these investigators." One reason is that "association studies undertaken in clinical settings are likely to provide misleading results" because participants often have "coexisting illnesses that may result in spurious associations with the condition being investigated," he said (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMe1109130]).

In addition, "defining GOLD stage 1 disease as a ratio of FEV₁ to forced vital capacity (FVC) of less than 0.7, applied to all age groups, may lead to overreporting of abnormal ratios in older age groups and underreporting of them in younger age groups," said Dr. Burney of the National Heart and Lung Institute, Imperial College, London.

"Failure to distinguish between FEV₁ as a sign of obstruction and FEV₁ as a marker of low FVC has caused much confusion, mostly due to failure to measure or report FVC. It is almost certainly responsible for the association between ventilator function and markers of systemic inflammation in the cross-sectional data for ECLIPSE and has similarly led to inflated associations of ‘obstruction’ with increased all-cause mortality and cardiovascular events in so-called normal populations," Dr. Burney wrote.

As with other studies, he continued, this one showed that those who quit smoking have no clear loss of lung function over time, compared with nonsmokers, adding to the body of evidence that quitting smoking can reduce the rate of decline of lung function. The important message from ECLIPSE is that it is never too late to derive benefit from quitting smoking, although patients derive more benefits by doing so earlier, he noted.

The study was supported by grants from GlaxoSmithKline to Dr. Vestbo and several coauthors. Some of the coauthors are employees of and own stock in GlaxoSmithKline. All coauthors reported ties to numerous pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, Novartis, and Pfizer.

Dr. Burney disclosed receiving consulting fees from GlaxoSmithKline and lecture fees from Pfizer and Boehringer Ingelheim.

The rate of change in forced expiratory volume in 1 second among patients with chronic obstructive pulmonary disease is highly variable, with the greatest rates of decline occurring among current smokers, patients with bronchodilator reversibility, and those with emphysema, according to an analysis of data from the ECLIPSE observational study reported online Sept. 26 in the New England Journal of Medicine.

Research in the 1970s established that patients with COPD experience an accelerated decline in FEV₁, yet few longitudinal studies have provided detailed data about this decline. Also, none have provided information about FEV₁ in specific subgroups of patients with COPD or according to levels of specific biomarkers.

Dr. Jørgen Vestbo of the University of Copenhagen and his colleagues analyzed data collected for the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, which included 2,163 patients aged 40-75 years who had a smoking history of 10 or more pack-years and 80% of the predicted value and ratio of FEV₁ to forced vital capacity (FVC) of 0.7 or less (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMoa1105482]).

Specifically, the researchers analyzed changes in FEV₁ after bronchodilator use at baseline, 3 months, 6 months, and then every 6 months for 3 years. They defined subgroups according to the presence of emphysema and chronic bronchitis, bronchodilator reversibility, and cardiovascular disease. They also obtained serum and plasma samples for the following biomarkers: C-reactive protein, interleukin-8, interleukin-6, fibrinogen, tumor necrosis factor–alpha, surfactant protein D, and Clara cell secretory protein 16 (CC-16).

The rate of FEV₁ was highly variable during the 3-year period, the results showed. Overall, there was a mean decline of 33 mL/year. More specifically, 38% of patients had a decline of more than 40 mL/year, 31% had a decline of 21-40 mL/year, 23% had changes ranging from a decline of 20 mL/year to an increase of 20 mL/year, and 8% had an increase of more than 20 mL/year.

The researchers also found an inverse relationship between the declines in FEV₁ and stage of disease, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Mean rates of decline were 35 mL/year in patients with moderate disease (GOLD stage 2), 33 mL/year in patients with severe disease (GOLD stage 3), and 25 mL/year in patients with very severe disease (GOLD stage 4).

Smoking status was most strongly associated with the rate of decline, with current smokers experiencing a decline of 21 mL/year more than former smokers. However, cumulative exposure did not affect future decline. "This finding points to smoking cessation as the most important tool in secondary and tertiary prevention for patients at all stages of COPD," the researchers said.

Among the subgroups studied, FEV₁ declined by 17 mL more per year in patients with bronchodilator reversibility at baseline, compared with those without reversibility. Also, FEV₁ declined by an additional 13 mL/year in patients with clinically significant emphysema versus those with little or no emphysema. The presence of cardiovascular disease had no effect on FEV₁.

Although several biomarkers were associated with FEV₁ at baseline, only CC-16 levels were significantly associated with the rate of change in FEV₁, with an additional decline of 4 mL/year for each decrease of 1 standard deviation in the level of CC-16. "This association was weak, and whether it is biologically meaningful has yet to be determined," Dr. Vestbo and his colleagues said. "Without confirmation, it does not seem appropriate to speculate on the potential significance of this finding."

The study findings call into question whether COPD is invariably progressive. "In more than half the patients in our study, the rate of decline in FEV₁ over a period of 3 years was no greater than that which has been observed in people without lung disease. This finding could indicate that COPD may ‘burn out’ or at least stabilize for periods of 3 years or more, which would be good news for patients and could influence a variety of management decisions that depend on prognosis."

A limitation of the study was that it included only patients with moderate, severe, or very severe COPD, and therefore could not identify factors associated with rates of decline in early-stage COPD. Also, the study was purely observational and did not include treatment. "Moreover, the diagnosis and management of COPD in the patients in our study were carried out at specialist centers, and our results may not extend beyond this patient population for a variety of reasons, including the clinically determined care they received," the researchers said.

In an editorial accompanying the report, Dr. Peter Burney said this longitudinal analysis "did not confirm the promise of the earlier cross-sectional analysis [Eur. Respir. J. 2008;31:869-73] by these investigators." One reason is that "association studies undertaken in clinical settings are likely to provide misleading results" because participants often have "coexisting illnesses that may result in spurious associations with the condition being investigated," he said (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMe1109130]).

In addition, "defining GOLD stage 1 disease as a ratio of FEV₁ to forced vital capacity (FVC) of less than 0.7, applied to all age groups, may lead to overreporting of abnormal ratios in older age groups and underreporting of them in younger age groups," said Dr. Burney of the National Heart and Lung Institute, Imperial College, London.

"Failure to distinguish between FEV₁ as a sign of obstruction and FEV₁ as a marker of low FVC has caused much confusion, mostly due to failure to measure or report FVC. It is almost certainly responsible for the association between ventilator function and markers of systemic inflammation in the cross-sectional data for ECLIPSE and has similarly led to inflated associations of ‘obstruction’ with increased all-cause mortality and cardiovascular events in so-called normal populations," Dr. Burney wrote.

As with other studies, he continued, this one showed that those who quit smoking have no clear loss of lung function over time, compared with nonsmokers, adding to the body of evidence that quitting smoking can reduce the rate of decline of lung function. The important message from ECLIPSE is that it is never too late to derive benefit from quitting smoking, although patients derive more benefits by doing so earlier, he noted.

The study was supported by grants from GlaxoSmithKline to Dr. Vestbo and several coauthors. Some of the coauthors are employees of and own stock in GlaxoSmithKline. All coauthors reported ties to numerous pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, Novartis, and Pfizer.

Dr. Burney disclosed receiving consulting fees from GlaxoSmithKline and lecture fees from Pfizer and Boehringer Ingelheim.

The rate of change in forced expiratory volume in 1 second among patients with chronic obstructive pulmonary disease is highly variable, with the greatest rates of decline occurring among current smokers, patients with bronchodilator reversibility, and those with emphysema, according to an analysis of data from the ECLIPSE observational study reported online Sept. 26 in the New England Journal of Medicine.

Research in the 1970s established that patients with COPD experience an accelerated decline in FEV₁, yet few longitudinal studies have provided detailed data about this decline. Also, none have provided information about FEV₁ in specific subgroups of patients with COPD or according to levels of specific biomarkers.

Dr. Jørgen Vestbo of the University of Copenhagen and his colleagues analyzed data collected for the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, which included 2,163 patients aged 40-75 years who had a smoking history of 10 or more pack-years and 80% of the predicted value and ratio of FEV₁ to forced vital capacity (FVC) of 0.7 or less (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMoa1105482]).

Specifically, the researchers analyzed changes in FEV₁ after bronchodilator use at baseline, 3 months, 6 months, and then every 6 months for 3 years. They defined subgroups according to the presence of emphysema and chronic bronchitis, bronchodilator reversibility, and cardiovascular disease. They also obtained serum and plasma samples for the following biomarkers: C-reactive protein, interleukin-8, interleukin-6, fibrinogen, tumor necrosis factor–alpha, surfactant protein D, and Clara cell secretory protein 16 (CC-16).

The rate of FEV₁ was highly variable during the 3-year period, the results showed. Overall, there was a mean decline of 33 mL/year. More specifically, 38% of patients had a decline of more than 40 mL/year, 31% had a decline of 21-40 mL/year, 23% had changes ranging from a decline of 20 mL/year to an increase of 20 mL/year, and 8% had an increase of more than 20 mL/year.

The researchers also found an inverse relationship between the declines in FEV₁ and stage of disease, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Mean rates of decline were 35 mL/year in patients with moderate disease (GOLD stage 2), 33 mL/year in patients with severe disease (GOLD stage 3), and 25 mL/year in patients with very severe disease (GOLD stage 4).

Smoking status was most strongly associated with the rate of decline, with current smokers experiencing a decline of 21 mL/year more than former smokers. However, cumulative exposure did not affect future decline. "This finding points to smoking cessation as the most important tool in secondary and tertiary prevention for patients at all stages of COPD," the researchers said.

Among the subgroups studied, FEV₁ declined by 17 mL more per year in patients with bronchodilator reversibility at baseline, compared with those without reversibility. Also, FEV₁ declined by an additional 13 mL/year in patients with clinically significant emphysema versus those with little or no emphysema. The presence of cardiovascular disease had no effect on FEV₁.

Although several biomarkers were associated with FEV₁ at baseline, only CC-16 levels were significantly associated with the rate of change in FEV₁, with an additional decline of 4 mL/year for each decrease of 1 standard deviation in the level of CC-16. "This association was weak, and whether it is biologically meaningful has yet to be determined," Dr. Vestbo and his colleagues said. "Without confirmation, it does not seem appropriate to speculate on the potential significance of this finding."

The study findings call into question whether COPD is invariably progressive. "In more than half the patients in our study, the rate of decline in FEV₁ over a period of 3 years was no greater than that which has been observed in people without lung disease. This finding could indicate that COPD may ‘burn out’ or at least stabilize for periods of 3 years or more, which would be good news for patients and could influence a variety of management decisions that depend on prognosis."

A limitation of the study was that it included only patients with moderate, severe, or very severe COPD, and therefore could not identify factors associated with rates of decline in early-stage COPD. Also, the study was purely observational and did not include treatment. "Moreover, the diagnosis and management of COPD in the patients in our study were carried out at specialist centers, and our results may not extend beyond this patient population for a variety of reasons, including the clinically determined care they received," the researchers said.

In an editorial accompanying the report, Dr. Peter Burney said this longitudinal analysis "did not confirm the promise of the earlier cross-sectional analysis [Eur. Respir. J. 2008;31:869-73] by these investigators." One reason is that "association studies undertaken in clinical settings are likely to provide misleading results" because participants often have "coexisting illnesses that may result in spurious associations with the condition being investigated," he said (N. Engl. J. Med. 2011 Sept. 26 [doi:10.1056/NEJMe1109130]).

In addition, "defining GOLD stage 1 disease as a ratio of FEV₁ to forced vital capacity (FVC) of less than 0.7, applied to all age groups, may lead to overreporting of abnormal ratios in older age groups and underreporting of them in younger age groups," said Dr. Burney of the National Heart and Lung Institute, Imperial College, London.

"Failure to distinguish between FEV₁ as a sign of obstruction and FEV₁ as a marker of low FVC has caused much confusion, mostly due to failure to measure or report FVC. It is almost certainly responsible for the association between ventilator function and markers of systemic inflammation in the cross-sectional data for ECLIPSE and has similarly led to inflated associations of ‘obstruction’ with increased all-cause mortality and cardiovascular events in so-called normal populations," Dr. Burney wrote.

As with other studies, he continued, this one showed that those who quit smoking have no clear loss of lung function over time, compared with nonsmokers, adding to the body of evidence that quitting smoking can reduce the rate of decline of lung function. The important message from ECLIPSE is that it is never too late to derive benefit from quitting smoking, although patients derive more benefits by doing so earlier, he noted.

The study was supported by grants from GlaxoSmithKline to Dr. Vestbo and several coauthors. Some of the coauthors are employees of and own stock in GlaxoSmithKline. All coauthors reported ties to numerous pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, Novartis, and Pfizer.

Dr. Burney disclosed receiving consulting fees from GlaxoSmithKline and lecture fees from Pfizer and Boehringer Ingelheim.

The experimental tyrosine kinase inhibitor BIBF 1120 was associated with a clinically meaningful reduction in the rate of decline in forced vital capacity, compared with placebo, in patients with idiopathic pulmonary fibrosis in a yearlong, phase II dose-ranging trial involving 432 patients.

Active treatment was also associated with a reduction in the incidence of acute exacerbations of the disease and with an increase in quality of life scores, compared with placebo, Dr. Luca Richeldi of the University of Modena (Italy) and Reggio Emilia, Policlinico Hospital, Modena, and his colleagues reported in the Sept. 22 issue of the New England Journal of Medicine.

Specifically, 85 patients randomized to receive an oral dose of BIBF 1120 at 150 mg twice daily had a mean decline in forced vital capacity (FVC) of 0.06 L/year, compared with 0.19 L/year in 83 patients randomized to receive placebo, a 68.4% reduction. This difference is not statistically significant but does approach the threshold for significance. Also, the absolute change in FVC from baseline over time in the treatment group, compared with the placebo group, was statistically significant, the investigators wrote (N. Engl. J. Med. 2011;365:1079-87).

Acute exacerbations occurred at a rate of 2.4 vs. 15.7 per 100 patient-years in the 150-mg twice-daily treatment group and the placebo group, respectively, a significant difference. There was a trend toward a dose response with increasing doses of BIBF 1120. In addition, scores on the St. George’s Respiratory Questionnaire (SGRQ) in the treated patients decreased by 0.66 points on a 0-100 scale, but increased by 5.46 points in the placebo group. This difference was also significant.

"There were improvements in two domains of the SGRQ – symptoms and activity – in the group receiving 150 mg of BIBF 1120 twice a day as compared with the placebo group (–3.14 points vs. 6.45 points and 0.32 points vs. 7.48 points, respectively), and there was a dose-dependent trend toward an improvement in the impact domain, which is a broad measure of the impact of respiratory disease on the patient," they said.

There was also a trend toward fewer deaths from respiratory causes in the 150-mg twice-daily treatment group and the 100-mg twice-daily group, with two such deaths in each of those groups, compared with nine and three deaths in the 50-mg once-daily and the 50-mg twice-daily groups, respectively, and eight in the placebo group.

Study participants were adults aged 40 years or older with high-resolution CT–confirmed idiopathic pulmonary fibrosis diagnosed within the previous 5 years. They were recruited from 92 sites in 25 countries, and were randomized in double-blind fashion to receive either placebo, 50 mg once daily, 50 mg twice daily, 100 mg twice daily, or 150 mg twice daily for 52 weeks.

As for adverse events, the overall incidence was similar in each of the groups, as was the incidence of serious and severe adverse events and adverse events requiring hospitalization. The proportion of patients with serious adverse events was lower in the 150-mg twice-daily treatment group than in the placebo group (27.1% vs. 30.6%), and the lowest proportion was in the 100-mg twice-daily group (14%). Most of the adverse events that led to discontinuation of treatment were gastrointestinal in nature, and included diarrhea, nausea, and vomiting. These occurred most often the 150-mg twice-daily group.

However, the number of fatal adverse events decreased with increasing doses of BIBF 1120, with 12, 10, 4, and 5 patients in the placebo, 50-mg once-daily, 50-mg twice-daily, and 100-mg twice-daily groups experiencing a fatal adverse event, and only 1 in the 150-mg twice-daily group experiencing a fatal adverse event.

While this trial failed to show a significant difference in the predefined multiplicity-corrected end point of the annual rate of decline in FVC, the findings nonetheless suggest that BIBF 1120 is a promising treatment for idiopathic pulmonary fibrosis, particularly given the seriousness of this condition and the paucity of therapeutic options, according to the investigators.

Further, the results of the secondary end point analyses support the 150-mg twice-daily dose – and for some end points, the 100-mg twice-daily dose, they noted.

A particularly important finding was the significantly lower incidence of acute exacerbations in the 150-mg twice-daily group, compared with the placebo group.

"This result is clinically important, since acute exacerbations are associated with rapid disease progression, a severe and abrupt decline in forced vital capacity, and high mortality," the investigators wrote.

This finding may have contributed to the higher quality of life scores seen in the higher-dosage groups than in the other groups, which had higher incidences of exacerbations, they added, concluding that the findings warrant additional investigation in phase III clinical studies.

The study by Dr. Richeldi and his colleagues was supported by Boehringer Ingelheim, which employs some of the study authors. More detailed disclosures are available with the full text of the article at NEJM.org.

The experimental tyrosine kinase inhibitor BIBF 1120 was associated with a clinically meaningful reduction in the rate of decline in forced vital capacity, compared with placebo, in patients with idiopathic pulmonary fibrosis in a yearlong, phase II dose-ranging trial involving 432 patients.

Active treatment was also associated with a reduction in the incidence of acute exacerbations of the disease and with an increase in quality of life scores, compared with placebo, Dr. Luca Richeldi of the University of Modena (Italy) and Reggio Emilia, Policlinico Hospital, Modena, and his colleagues reported in the Sept. 22 issue of the New England Journal of Medicine.

Specifically, 85 patients randomized to receive an oral dose of BIBF 1120 at 150 mg twice daily had a mean decline in forced vital capacity (FVC) of 0.06 L/year, compared with 0.19 L/year in 83 patients randomized to receive placebo, a 68.4% reduction. This difference is not statistically significant but does approach the threshold for significance. Also, the absolute change in FVC from baseline over time in the treatment group, compared with the placebo group, was statistically significant, the investigators wrote (N. Engl. J. Med. 2011;365:1079-87).

Acute exacerbations occurred at a rate of 2.4 vs. 15.7 per 100 patient-years in the 150-mg twice-daily treatment group and the placebo group, respectively, a significant difference. There was a trend toward a dose response with increasing doses of BIBF 1120. In addition, scores on the St. George’s Respiratory Questionnaire (SGRQ) in the treated patients decreased by 0.66 points on a 0-100 scale, but increased by 5.46 points in the placebo group. This difference was also significant.

"There were improvements in two domains of the SGRQ – symptoms and activity – in the group receiving 150 mg of BIBF 1120 twice a day as compared with the placebo group (–3.14 points vs. 6.45 points and 0.32 points vs. 7.48 points, respectively), and there was a dose-dependent trend toward an improvement in the impact domain, which is a broad measure of the impact of respiratory disease on the patient," they said.

There was also a trend toward fewer deaths from respiratory causes in the 150-mg twice-daily treatment group and the 100-mg twice-daily group, with two such deaths in each of those groups, compared with nine and three deaths in the 50-mg once-daily and the 50-mg twice-daily groups, respectively, and eight in the placebo group.

Study participants were adults aged 40 years or older with high-resolution CT–confirmed idiopathic pulmonary fibrosis diagnosed within the previous 5 years. They were recruited from 92 sites in 25 countries, and were randomized in double-blind fashion to receive either placebo, 50 mg once daily, 50 mg twice daily, 100 mg twice daily, or 150 mg twice daily for 52 weeks.

As for adverse events, the overall incidence was similar in each of the groups, as was the incidence of serious and severe adverse events and adverse events requiring hospitalization. The proportion of patients with serious adverse events was lower in the 150-mg twice-daily treatment group than in the placebo group (27.1% vs. 30.6%), and the lowest proportion was in the 100-mg twice-daily group (14%). Most of the adverse events that led to discontinuation of treatment were gastrointestinal in nature, and included diarrhea, nausea, and vomiting. These occurred most often the 150-mg twice-daily group.

However, the number of fatal adverse events decreased with increasing doses of BIBF 1120, with 12, 10, 4, and 5 patients in the placebo, 50-mg once-daily, 50-mg twice-daily, and 100-mg twice-daily groups experiencing a fatal adverse event, and only 1 in the 150-mg twice-daily group experiencing a fatal adverse event.

While this trial failed to show a significant difference in the predefined multiplicity-corrected end point of the annual rate of decline in FVC, the findings nonetheless suggest that BIBF 1120 is a promising treatment for idiopathic pulmonary fibrosis, particularly given the seriousness of this condition and the paucity of therapeutic options, according to the investigators.

Further, the results of the secondary end point analyses support the 150-mg twice-daily dose – and for some end points, the 100-mg twice-daily dose, they noted.

A particularly important finding was the significantly lower incidence of acute exacerbations in the 150-mg twice-daily group, compared with the placebo group.

"This result is clinically important, since acute exacerbations are associated with rapid disease progression, a severe and abrupt decline in forced vital capacity, and high mortality," the investigators wrote.

This finding may have contributed to the higher quality of life scores seen in the higher-dosage groups than in the other groups, which had higher incidences of exacerbations, they added, concluding that the findings warrant additional investigation in phase III clinical studies.

The study by Dr. Richeldi and his colleagues was supported by Boehringer Ingelheim, which employs some of the study authors. More detailed disclosures are available with the full text of the article at NEJM.org.

The experimental tyrosine kinase inhibitor BIBF 1120 was associated with a clinically meaningful reduction in the rate of decline in forced vital capacity, compared with placebo, in patients with idiopathic pulmonary fibrosis in a yearlong, phase II dose-ranging trial involving 432 patients.

Active treatment was also associated with a reduction in the incidence of acute exacerbations of the disease and with an increase in quality of life scores, compared with placebo, Dr. Luca Richeldi of the University of Modena (Italy) and Reggio Emilia, Policlinico Hospital, Modena, and his colleagues reported in the Sept. 22 issue of the New England Journal of Medicine.

Specifically, 85 patients randomized to receive an oral dose of BIBF 1120 at 150 mg twice daily had a mean decline in forced vital capacity (FVC) of 0.06 L/year, compared with 0.19 L/year in 83 patients randomized to receive placebo, a 68.4% reduction. This difference is not statistically significant but does approach the threshold for significance. Also, the absolute change in FVC from baseline over time in the treatment group, compared with the placebo group, was statistically significant, the investigators wrote (N. Engl. J. Med. 2011;365:1079-87).

Acute exacerbations occurred at a rate of 2.4 vs. 15.7 per 100 patient-years in the 150-mg twice-daily treatment group and the placebo group, respectively, a significant difference. There was a trend toward a dose response with increasing doses of BIBF 1120. In addition, scores on the St. George’s Respiratory Questionnaire (SGRQ) in the treated patients decreased by 0.66 points on a 0-100 scale, but increased by 5.46 points in the placebo group. This difference was also significant.

"There were improvements in two domains of the SGRQ – symptoms and activity – in the group receiving 150 mg of BIBF 1120 twice a day as compared with the placebo group (–3.14 points vs. 6.45 points and 0.32 points vs. 7.48 points, respectively), and there was a dose-dependent trend toward an improvement in the impact domain, which is a broad measure of the impact of respiratory disease on the patient," they said.

There was also a trend toward fewer deaths from respiratory causes in the 150-mg twice-daily treatment group and the 100-mg twice-daily group, with two such deaths in each of those groups, compared with nine and three deaths in the 50-mg once-daily and the 50-mg twice-daily groups, respectively, and eight in the placebo group.

Study participants were adults aged 40 years or older with high-resolution CT–confirmed idiopathic pulmonary fibrosis diagnosed within the previous 5 years. They were recruited from 92 sites in 25 countries, and were randomized in double-blind fashion to receive either placebo, 50 mg once daily, 50 mg twice daily, 100 mg twice daily, or 150 mg twice daily for 52 weeks.

As for adverse events, the overall incidence was similar in each of the groups, as was the incidence of serious and severe adverse events and adverse events requiring hospitalization. The proportion of patients with serious adverse events was lower in the 150-mg twice-daily treatment group than in the placebo group (27.1% vs. 30.6%), and the lowest proportion was in the 100-mg twice-daily group (14%). Most of the adverse events that led to discontinuation of treatment were gastrointestinal in nature, and included diarrhea, nausea, and vomiting. These occurred most often the 150-mg twice-daily group.

However, the number of fatal adverse events decreased with increasing doses of BIBF 1120, with 12, 10, 4, and 5 patients in the placebo, 50-mg once-daily, 50-mg twice-daily, and 100-mg twice-daily groups experiencing a fatal adverse event, and only 1 in the 150-mg twice-daily group experiencing a fatal adverse event.

While this trial failed to show a significant difference in the predefined multiplicity-corrected end point of the annual rate of decline in FVC, the findings nonetheless suggest that BIBF 1120 is a promising treatment for idiopathic pulmonary fibrosis, particularly given the seriousness of this condition and the paucity of therapeutic options, according to the investigators.

Further, the results of the secondary end point analyses support the 150-mg twice-daily dose – and for some end points, the 100-mg twice-daily dose, they noted.

A particularly important finding was the significantly lower incidence of acute exacerbations in the 150-mg twice-daily group, compared with the placebo group.

"This result is clinically important, since acute exacerbations are associated with rapid disease progression, a severe and abrupt decline in forced vital capacity, and high mortality," the investigators wrote.

This finding may have contributed to the higher quality of life scores seen in the higher-dosage groups than in the other groups, which had higher incidences of exacerbations, they added, concluding that the findings warrant additional investigation in phase III clinical studies.

The study by Dr. Richeldi and his colleagues was supported by Boehringer Ingelheim, which employs some of the study authors. More detailed disclosures are available with the full text of the article at NEJM.org.

Low gestational age at birth appears to be strongly associated with higher mortality during young adulthood, independently of fetal growth and other perinatal and socioeconomic factors, according to a study in the Sept. 21 issue of JAMA.

The robust association was observed even among "late" preterm births at 34-36 weeks, said Dr. Casey Crump of the department of medicine at Stanford (Calif.) University, and his associates.

© AndyL/iStockphoto.com

"To our knowledge, this is the first study to report the specific contribution of gestational age at birth on mortality in adulthood. The results underscore the persistent long-term health sequelae of preterm birth," the investigators said (JAMA 2011;306:1233-40).

"Clinicians will increasingly encounter the health sequelae of preterm birth throughout the life course and will need to be aware of the long-term effects on the survivors, their families, and society," they noted.

Previous studies have examined the relationship between low birth weight and adult mortality, but have not assessed the contribution of gestational age. To do so, Dr. Crump and his colleagues performed a cohort study of 674,820 singleton infants born in 1973-1979 in Sweden, who were followed throughout their lives for all-cause and cause-specific mortality.

The study subjects were aged 29-36 years at the most recent follow-up. The prevalence of preterm birth in Sweden in the late 1970s was 5%. The prevalence in this cohort was 4.1% (27,979 preterm births).

There were 7,095 deaths among the study subjects. Mortality strongly correlated with low gestational age (LGA) at birth during early childhood, an association that disappeared in late childhood and adolescence but reappeared in young adulthood.

The relationship was robust and linear in young adulthood at ages 18-36 years. Adjusting the data to account for numerous possible confounders – including the subject’s sex, birth year, and birth order; the mother’s age at delivery; the mother’s marital status; and both parents’ educational status – had little effect on the risk estimates.

An analysis that excluded subjects born with congenital malformations also did not affect the correlation between LGA at birth and increased mortality in young adulthood. Mortality was increased even among subjects born at the end of the preterm period at 34-36 weeks, the investigators said.

When the data were analyzed by cause of death, LGA at birth was most strongly associated with mortality due to respiratory and endocrine disorders, followed by cardiovascular disorders. In contrast, it was not significantly associated with death from neurological disorders, cancer, or injury.

This finding is consistent with reports in the literature that LGA correlates with asthma, hypertension, diabetes, and hypothyroidism in later life, Dr. Crump and his associates said.

"The underlying mechanisms are still largely unknown but may involve a complex interplay of fetal and postnatal nutritional abnormalities; other intrauterine exposures, including glucocorticoid and sex hormone alterations; and common genetic factors," they said.

The researchers noted that the prevalence of preterm birth in the United States at present exceeds 12%, more than double the prevalence in this cohort. Most survivors "have a high level of function and self-reported quality of life," but the results of this study show that increased long-term morbidities and mortality also can be expected, Dr. Crump and his associates said.

However, it should be noted that today’s preterm infants may differ in important ways from the subjects in this study because neonatal care has advanced during the interim. "It is unclear to what extent our findings are generalizable to later cohorts, and any such comparison should be made with caution," they noted.

This study was supported by the U.S. National Institute of Child Health and Human Development, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research), Lund, Sweden. The authors reported no financial conflicts of interest.

Low gestational age at birth appears to be strongly associated with higher mortality during young adulthood, independently of fetal growth and other perinatal and socioeconomic factors, according to a study in the Sept. 21 issue of JAMA.

The robust association was observed even among "late" preterm births at 34-36 weeks, said Dr. Casey Crump of the department of medicine at Stanford (Calif.) University, and his associates.

© AndyL/iStockphoto.com

"To our knowledge, this is the first study to report the specific contribution of gestational age at birth on mortality in adulthood. The results underscore the persistent long-term health sequelae of preterm birth," the investigators said (JAMA 2011;306:1233-40).

"Clinicians will increasingly encounter the health sequelae of preterm birth throughout the life course and will need to be aware of the long-term effects on the survivors, their families, and society," they noted.

Previous studies have examined the relationship between low birth weight and adult mortality, but have not assessed the contribution of gestational age. To do so, Dr. Crump and his colleagues performed a cohort study of 674,820 singleton infants born in 1973-1979 in Sweden, who were followed throughout their lives for all-cause and cause-specific mortality.

The study subjects were aged 29-36 years at the most recent follow-up. The prevalence of preterm birth in Sweden in the late 1970s was 5%. The prevalence in this cohort was 4.1% (27,979 preterm births).

There were 7,095 deaths among the study subjects. Mortality strongly correlated with low gestational age (LGA) at birth during early childhood, an association that disappeared in late childhood and adolescence but reappeared in young adulthood.

The relationship was robust and linear in young adulthood at ages 18-36 years. Adjusting the data to account for numerous possible confounders – including the subject’s sex, birth year, and birth order; the mother’s age at delivery; the mother’s marital status; and both parents’ educational status – had little effect on the risk estimates.

An analysis that excluded subjects born with congenital malformations also did not affect the correlation between LGA at birth and increased mortality in young adulthood. Mortality was increased even among subjects born at the end of the preterm period at 34-36 weeks, the investigators said.

When the data were analyzed by cause of death, LGA at birth was most strongly associated with mortality due to respiratory and endocrine disorders, followed by cardiovascular disorders. In contrast, it was not significantly associated with death from neurological disorders, cancer, or injury.

This finding is consistent with reports in the literature that LGA correlates with asthma, hypertension, diabetes, and hypothyroidism in later life, Dr. Crump and his associates said.

"The underlying mechanisms are still largely unknown but may involve a complex interplay of fetal and postnatal nutritional abnormalities; other intrauterine exposures, including glucocorticoid and sex hormone alterations; and common genetic factors," they said.

The researchers noted that the prevalence of preterm birth in the United States at present exceeds 12%, more than double the prevalence in this cohort. Most survivors "have a high level of function and self-reported quality of life," but the results of this study show that increased long-term morbidities and mortality also can be expected, Dr. Crump and his associates said.

However, it should be noted that today’s preterm infants may differ in important ways from the subjects in this study because neonatal care has advanced during the interim. "It is unclear to what extent our findings are generalizable to later cohorts, and any such comparison should be made with caution," they noted.

This study was supported by the U.S. National Institute of Child Health and Human Development, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research), Lund, Sweden. The authors reported no financial conflicts of interest.

Low gestational age at birth appears to be strongly associated with higher mortality during young adulthood, independently of fetal growth and other perinatal and socioeconomic factors, according to a study in the Sept. 21 issue of JAMA.

The robust association was observed even among "late" preterm births at 34-36 weeks, said Dr. Casey Crump of the department of medicine at Stanford (Calif.) University, and his associates.

© AndyL/iStockphoto.com

"To our knowledge, this is the first study to report the specific contribution of gestational age at birth on mortality in adulthood. The results underscore the persistent long-term health sequelae of preterm birth," the investigators said (JAMA 2011;306:1233-40).

"Clinicians will increasingly encounter the health sequelae of preterm birth throughout the life course and will need to be aware of the long-term effects on the survivors, their families, and society," they noted.

Previous studies have examined the relationship between low birth weight and adult mortality, but have not assessed the contribution of gestational age. To do so, Dr. Crump and his colleagues performed a cohort study of 674,820 singleton infants born in 1973-1979 in Sweden, who were followed throughout their lives for all-cause and cause-specific mortality.

The study subjects were aged 29-36 years at the most recent follow-up. The prevalence of preterm birth in Sweden in the late 1970s was 5%. The prevalence in this cohort was 4.1% (27,979 preterm births).

There were 7,095 deaths among the study subjects. Mortality strongly correlated with low gestational age (LGA) at birth during early childhood, an association that disappeared in late childhood and adolescence but reappeared in young adulthood.

The relationship was robust and linear in young adulthood at ages 18-36 years. Adjusting the data to account for numerous possible confounders – including the subject’s sex, birth year, and birth order; the mother’s age at delivery; the mother’s marital status; and both parents’ educational status – had little effect on the risk estimates.

An analysis that excluded subjects born with congenital malformations also did not affect the correlation between LGA at birth and increased mortality in young adulthood. Mortality was increased even among subjects born at the end of the preterm period at 34-36 weeks, the investigators said.

When the data were analyzed by cause of death, LGA at birth was most strongly associated with mortality due to respiratory and endocrine disorders, followed by cardiovascular disorders. In contrast, it was not significantly associated with death from neurological disorders, cancer, or injury.

This finding is consistent with reports in the literature that LGA correlates with asthma, hypertension, diabetes, and hypothyroidism in later life, Dr. Crump and his associates said.

"The underlying mechanisms are still largely unknown but may involve a complex interplay of fetal and postnatal nutritional abnormalities; other intrauterine exposures, including glucocorticoid and sex hormone alterations; and common genetic factors," they said.

The researchers noted that the prevalence of preterm birth in the United States at present exceeds 12%, more than double the prevalence in this cohort. Most survivors "have a high level of function and self-reported quality of life," but the results of this study show that increased long-term morbidities and mortality also can be expected, Dr. Crump and his associates said.

However, it should be noted that today’s preterm infants may differ in important ways from the subjects in this study because neonatal care has advanced during the interim. "It is unclear to what extent our findings are generalizable to later cohorts, and any such comparison should be made with caution," they noted.

This study was supported by the U.S. National Institute of Child Health and Human Development, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research), Lund, Sweden. The authors reported no financial conflicts of interest.

Children who are treated with selective serotonin reuptake inhibitors have fivefold greater odds of experiencing periodic limb movements of sleep than do those who are not treated with SSRIs, according to findings from a retrospective review of polysomnography data.

Nearly a third (31.7%) of 41 children receiving SSRIs at the time of the study experienced periodic limb movements of sleep, compared with only 7.8% of 982 children not receiving SSRIs (odds ratio, 5.45), Dr. Martina Vendrame of Boston University and her colleagues reported.

Furthermore, the median periodic limb movement index in those receiving SSRIs was significantly higher than the index in those not receiving SSRIs (11.2 vs. 6.5), the investigators said (Pediatr. Neurol. 2011;45:175-7).

Although periodic limb movements of sleep have been reported in adults taking serotonergic antidepressants – with one study showing that 44% of adults receiving fluoxetine experienced the symptoms, and others showing that restless legs syndrome (RLS) is exacerbated in up to 10% of adult patients on SSRIs – the current study is one of few that provide information about periodic limb movements of sleep in children and adolescents.

Study subjects were all children who underwent overnight diagnostic polysomnography between January 2009 and April 2010 at a single center. The studies were conducted for various sleep disturbances such as snoring, pauses in breathing, daytime sleepiness, and gasping or snorting in sleep; none was conducted for reports of RLS or periodic limb movements of sleep.

The patients who received SSRIs included 31 girls and 10 boys who had a median age of 15.4 years. The SSRIs were prescribed for depression and included citalopram or escitalopram in 15 patients, fluoxetine in 14 patients, and sertraline in 12 patients.

"The mechanism by which SSRIs may cause periodic limb movements of sleep is not clear, but serotonin-mediated dopaminergic inhibition may represent the underlying mechanism," the investigators noted.

Although no significant differences in mean periodic limb movements of sleep indices were seen between different SSRIs in this study, it is possible that different doses and timing of administration could result in better control of limb movements, they said, adding that when periodic limb movements of sleep are found, a careful history should be taken to assess whether they are causing sleep disturbance, and also to determine if the child is experiencing RLS.

"If necessary, the use of antidepressants not associated with periodic limb movements of sleep should be considered," they wrote.

Although limited by the use of single-night polysomnography, a small study population, and possibly by referral bias to a tertiary center, the findings suggest that periodic limb movements of sleep may be an important side effect of SSRIs that is frequently overlooked in children.

"Recognition may result in better control of periodic limb movements of sleep and improved quality of life in these patients," they concluded, noting that future investigations should include a multicenter, prospective study using multinight polysomnography, investigation of various SSRIs separately, and evaluation of the role of underlying diseases for which subjects are treated with antidepressants in the development of periodic limb movements of sleep.

No financial disclosure information was available in the report.

Children who are treated with selective serotonin reuptake inhibitors have fivefold greater odds of experiencing periodic limb movements of sleep than do those who are not treated with SSRIs, according to findings from a retrospective review of polysomnography data.

Nearly a third (31.7%) of 41 children receiving SSRIs at the time of the study experienced periodic limb movements of sleep, compared with only 7.8% of 982 children not receiving SSRIs (odds ratio, 5.45), Dr. Martina Vendrame of Boston University and her colleagues reported.

Furthermore, the median periodic limb movement index in those receiving SSRIs was significantly higher than the index in those not receiving SSRIs (11.2 vs. 6.5), the investigators said (Pediatr. Neurol. 2011;45:175-7).

Although periodic limb movements of sleep have been reported in adults taking serotonergic antidepressants – with one study showing that 44% of adults receiving fluoxetine experienced the symptoms, and others showing that restless legs syndrome (RLS) is exacerbated in up to 10% of adult patients on SSRIs – the current study is one of few that provide information about periodic limb movements of sleep in children and adolescents.

Study subjects were all children who underwent overnight diagnostic polysomnography between January 2009 and April 2010 at a single center. The studies were conducted for various sleep disturbances such as snoring, pauses in breathing, daytime sleepiness, and gasping or snorting in sleep; none was conducted for reports of RLS or periodic limb movements of sleep.

The patients who received SSRIs included 31 girls and 10 boys who had a median age of 15.4 years. The SSRIs were prescribed for depression and included citalopram or escitalopram in 15 patients, fluoxetine in 14 patients, and sertraline in 12 patients.

"The mechanism by which SSRIs may cause periodic limb movements of sleep is not clear, but serotonin-mediated dopaminergic inhibition may represent the underlying mechanism," the investigators noted.

Although no significant differences in mean periodic limb movements of sleep indices were seen between different SSRIs in this study, it is possible that different doses and timing of administration could result in better control of limb movements, they said, adding that when periodic limb movements of sleep are found, a careful history should be taken to assess whether they are causing sleep disturbance, and also to determine if the child is experiencing RLS.

"If necessary, the use of antidepressants not associated with periodic limb movements of sleep should be considered," they wrote.

Although limited by the use of single-night polysomnography, a small study population, and possibly by referral bias to a tertiary center, the findings suggest that periodic limb movements of sleep may be an important side effect of SSRIs that is frequently overlooked in children.

"Recognition may result in better control of periodic limb movements of sleep and improved quality of life in these patients," they concluded, noting that future investigations should include a multicenter, prospective study using multinight polysomnography, investigation of various SSRIs separately, and evaluation of the role of underlying diseases for which subjects are treated with antidepressants in the development of periodic limb movements of sleep.

No financial disclosure information was available in the report.

Children who are treated with selective serotonin reuptake inhibitors have fivefold greater odds of experiencing periodic limb movements of sleep than do those who are not treated with SSRIs, according to findings from a retrospective review of polysomnography data.

Nearly a third (31.7%) of 41 children receiving SSRIs at the time of the study experienced periodic limb movements of sleep, compared with only 7.8% of 982 children not receiving SSRIs (odds ratio, 5.45), Dr. Martina Vendrame of Boston University and her colleagues reported.

Furthermore, the median periodic limb movement index in those receiving SSRIs was significantly higher than the index in those not receiving SSRIs (11.2 vs. 6.5), the investigators said (Pediatr. Neurol. 2011;45:175-7).

Although periodic limb movements of sleep have been reported in adults taking serotonergic antidepressants – with one study showing that 44% of adults receiving fluoxetine experienced the symptoms, and others showing that restless legs syndrome (RLS) is exacerbated in up to 10% of adult patients on SSRIs – the current study is one of few that provide information about periodic limb movements of sleep in children and adolescents.

Study subjects were all children who underwent overnight diagnostic polysomnography between January 2009 and April 2010 at a single center. The studies were conducted for various sleep disturbances such as snoring, pauses in breathing, daytime sleepiness, and gasping or snorting in sleep; none was conducted for reports of RLS or periodic limb movements of sleep.

The patients who received SSRIs included 31 girls and 10 boys who had a median age of 15.4 years. The SSRIs were prescribed for depression and included citalopram or escitalopram in 15 patients, fluoxetine in 14 patients, and sertraline in 12 patients.

"The mechanism by which SSRIs may cause periodic limb movements of sleep is not clear, but serotonin-mediated dopaminergic inhibition may represent the underlying mechanism," the investigators noted.

Although no significant differences in mean periodic limb movements of sleep indices were seen between different SSRIs in this study, it is possible that different doses and timing of administration could result in better control of limb movements, they said, adding that when periodic limb movements of sleep are found, a careful history should be taken to assess whether they are causing sleep disturbance, and also to determine if the child is experiencing RLS.

"If necessary, the use of antidepressants not associated with periodic limb movements of sleep should be considered," they wrote.

Although limited by the use of single-night polysomnography, a small study population, and possibly by referral bias to a tertiary center, the findings suggest that periodic limb movements of sleep may be an important side effect of SSRIs that is frequently overlooked in children.

"Recognition may result in better control of periodic limb movements of sleep and improved quality of life in these patients," they concluded, noting that future investigations should include a multicenter, prospective study using multinight polysomnography, investigation of various SSRIs separately, and evaluation of the role of underlying diseases for which subjects are treated with antidepressants in the development of periodic limb movements of sleep.

No financial disclosure information was available in the report.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

California may be among the leading states in tobacco control, but it appears that the use of hookahs—water pipes for smoking tobacco—have been flying under the radar of policymakers for several years.

In fact, a new study from researchers at the University of California, San Diego School of Medicine found that between 2005 and 2008 hookah use among adults in the state increased by more than 40%.

Photo credit: Flickr user quinn.anya by Creative Commons License

“Though public indoor cigarette smoking is banned throughout California, hookah use is permitted in designated lounges,” lead investigator Dr. Wael K. Al-Delaimy, associate professor and chief of the Division of Global Health in the UCSD Department of Family and Preventive Medicine, said in a prepared statement. “This may create the impression that hookah is a safer alternative to cigarettes, which is simply not true.”

For the study, which appeared online Aug. 18 in the American Journal of Public Health, the researchers examined data from the California Tobacco Surveys, which are conducted statewide under Dr. Al-Delaimy’s direction. By 2008, hookah use in California was much higher among young adults aged 18-24 years (25% percent among men, 10% among women) than it was among all adults (11% among men, 3% percent among women). Rates of hookah smoking were highest among non-Hispanic whites who had at least some college education.

“More specific studies are warranted but we urge policymakers to consider laws that would ban hookah lounges, thus eliminating the implication that hookah smoking is safer and more socially acceptable than cigarette smoking,” Dr. Al-Delaimy said.

Dr. Al-Delaimy and his colleague, Joshua R. Smith, Ph.D., discussed the study’s findings in a video which can be viewed here.

Data collection for the study was funded by the California Department of Health Services. 

— Doug Brunk (on Twitter@dougbrunk)

California may be among the leading states in tobacco control, but it appears that the use of hookahs—water pipes for smoking tobacco—have been flying under the radar of policymakers for several years.

In fact, a new study from researchers at the University of California, San Diego School of Medicine found that between 2005 and 2008 hookah use among adults in the state increased by more than 40%.

Photo credit: Flickr user quinn.anya by Creative Commons License

“Though public indoor cigarette smoking is banned throughout California, hookah use is permitted in designated lounges,” lead investigator Dr. Wael K. Al-Delaimy, associate professor and chief of the Division of Global Health in the UCSD Department of Family and Preventive Medicine, said in a prepared statement. “This may create the impression that hookah is a safer alternative to cigarettes, which is simply not true.”

For the study, which appeared online Aug. 18 in the American Journal of Public Health, the researchers examined data from the California Tobacco Surveys, which are conducted statewide under Dr. Al-Delaimy’s direction. By 2008, hookah use in California was much higher among young adults aged 18-24 years (25% percent among men, 10% among women) than it was among all adults (11% among men, 3% percent among women). Rates of hookah smoking were highest among non-Hispanic whites who had at least some college education.

“More specific studies are warranted but we urge policymakers to consider laws that would ban hookah lounges, thus eliminating the implication that hookah smoking is safer and more socially acceptable than cigarette smoking,” Dr. Al-Delaimy said.

Dr. Al-Delaimy and his colleague, Joshua R. Smith, Ph.D., discussed the study’s findings in a video which can be viewed here.

Data collection for the study was funded by the California Department of Health Services. 

— Doug Brunk (on Twitter@dougbrunk)

California may be among the leading states in tobacco control, but it appears that the use of hookahs—water pipes for smoking tobacco—have been flying under the radar of policymakers for several years.

In fact, a new study from researchers at the University of California, San Diego School of Medicine found that between 2005 and 2008 hookah use among adults in the state increased by more than 40%.

Photo credit: Flickr user quinn.anya by Creative Commons License

“Though public indoor cigarette smoking is banned throughout California, hookah use is permitted in designated lounges,” lead investigator Dr. Wael K. Al-Delaimy, associate professor and chief of the Division of Global Health in the UCSD Department of Family and Preventive Medicine, said in a prepared statement. “This may create the impression that hookah is a safer alternative to cigarettes, which is simply not true.”

For the study, which appeared online Aug. 18 in the American Journal of Public Health, the researchers examined data from the California Tobacco Surveys, which are conducted statewide under Dr. Al-Delaimy’s direction. By 2008, hookah use in California was much higher among young adults aged 18-24 years (25% percent among men, 10% among women) than it was among all adults (11% among men, 3% percent among women). Rates of hookah smoking were highest among non-Hispanic whites who had at least some college education.

“More specific studies are warranted but we urge policymakers to consider laws that would ban hookah lounges, thus eliminating the implication that hookah smoking is safer and more socially acceptable than cigarette smoking,” Dr. Al-Delaimy said.

Dr. Al-Delaimy and his colleague, Joshua R. Smith, Ph.D., discussed the study’s findings in a video which can be viewed here.

Data collection for the study was funded by the California Department of Health Services. 

— Doug Brunk (on Twitter@dougbrunk)

In the months and years since the attacks of Sept. 11, 2001, the questions have not stopped and the answers have not always been forthcoming. What exactly were the physical and mental effects on those who survived the attacks? What about those who were first responders? Or volunteers who helped clear rubble at the World Trade Center site?

And what has been the impact on people whose family, friends, or co-workers perished on that day in New York, at the Pentagon or in Shanksville, Pa.?

Courtesy Wikimedia Comomns/U.S. Navy/Creative Commons License

On Thursday, Sept. 8, a few days shy of the 10th anniversary of yet another day that will live in infamy, the federal government announced that it was appointing a panel of experts to help advise the WTC Health Program on these issues.

It’s not that they were going entirely unaddressed, but there has been a hodgepodge of efforts, not all of them well-funded or comprehensive. Will this new program with its new slate of scientific advisers be able to provide better answers? Only time will tell.

The WTC Health Program came into existence in July, thanks to the James Zadroga 9/11 Health and Compensation Act of 2010. Named after a police detective who worked at Ground Zero and later died from a respiratory illness in 2006, the bill barely made it into law.

This New York Times article explains some of the back story–Senate Republicans worried that the U.S. would not be able to afford the law’s estimated $7.4 billion cost. That included $3.2 billion over the next 8 years to monitor and treat anyone who worked at the WTC site, and $4.2 billion to the September 11th Victim Compensation Fund.

The Times said that some 60,000 people had already participated in the World Trade Center (WTC) Medical Monitoring and Treatment Program (MMTP). That program was primarily available to response and recovery workers at the WTC site.

The city of New York has been actively monitoring and treating 9-11 survivors. It maintains a detailed list of possible health effects. And most of the MMTP sites were in New York.

The new law goes further, reaching out to others who were at the Pentagon and in Shanksville, and also to residents and workers who were in buildings close to the Twin Towers that day and in the days afterward. The Zadroga Act also puts a higher premium on research and epidemiology.

The 15-member World Trade Center Health Program’s Scientific/Technical Advisory Committee will help shape the research agenda and determine whether more health conditions need to be included in the monitoring and treatment rubric. The panel includes toxicologists, occupational physicians, a pulmonologist, experts in environmental health, a psychiatrist, and two representatives of WTC responders.

The program’s administrator, John Howard, said in the announcement that, “Independent expert scientific advice from the panel will be essential when complex scientific questions arise, and this panel represents the best of the field.”

Howard came under fire in late July when he announced the decision that the program would not pay for cancer-related expenses. That decision may be one of the first to be reviewed by the panel, which will begin meeting in New York in the fall. The advisory committee’s recommendations are just that, apparently. As of now, the program’s administrator has discretion to follow or ignore the panel’s advice.

Once the public meetings begin, the proceedings and recommendations will be available  on the WTC Health Program website.

—Alicia Ault (on Twitter @aliciaault)

In the months and years since the attacks of Sept. 11, 2001, the questions have not stopped and the answers have not always been forthcoming. What exactly were the physical and mental effects on those who survived the attacks? What about those who were first responders? Or volunteers who helped clear rubble at the World Trade Center site?

And what has been the impact on people whose family, friends, or co-workers perished on that day in New York, at the Pentagon or in Shanksville, Pa.?

Courtesy Wikimedia Comomns/U.S. Navy/Creative Commons License

On Thursday, Sept. 8, a few days shy of the 10th anniversary of yet another day that will live in infamy, the federal government announced that it was appointing a panel of experts to help advise the WTC Health Program on these issues.

It’s not that they were going entirely unaddressed, but there has been a hodgepodge of efforts, not all of them well-funded or comprehensive. Will this new program with its new slate of scientific advisers be able to provide better answers? Only time will tell.

The WTC Health Program came into existence in July, thanks to the James Zadroga 9/11 Health and Compensation Act of 2010. Named after a police detective who worked at Ground Zero and later died from a respiratory illness in 2006, the bill barely made it into law.

This New York Times article explains some of the back story–Senate Republicans worried that the U.S. would not be able to afford the law’s estimated $7.4 billion cost. That included $3.2 billion over the next 8 years to monitor and treat anyone who worked at the WTC site, and $4.2 billion to the September 11th Victim Compensation Fund.

The Times said that some 60,000 people had already participated in the World Trade Center (WTC) Medical Monitoring and Treatment Program (MMTP). That program was primarily available to response and recovery workers at the WTC site.

The city of New York has been actively monitoring and treating 9-11 survivors. It maintains a detailed list of possible health effects. And most of the MMTP sites were in New York.

The new law goes further, reaching out to others who were at the Pentagon and in Shanksville, and also to residents and workers who were in buildings close to the Twin Towers that day and in the days afterward. The Zadroga Act also puts a higher premium on research and epidemiology.

The 15-member World Trade Center Health Program’s Scientific/Technical Advisory Committee will help shape the research agenda and determine whether more health conditions need to be included in the monitoring and treatment rubric. The panel includes toxicologists, occupational physicians, a pulmonologist, experts in environmental health, a psychiatrist, and two representatives of WTC responders.

The program’s administrator, John Howard, said in the announcement that, “Independent expert scientific advice from the panel will be essential when complex scientific questions arise, and this panel represents the best of the field.”

Howard came under fire in late July when he announced the decision that the program would not pay for cancer-related expenses. That decision may be one of the first to be reviewed by the panel, which will begin meeting in New York in the fall. The advisory committee’s recommendations are just that, apparently. As of now, the program’s administrator has discretion to follow or ignore the panel’s advice.

Once the public meetings begin, the proceedings and recommendations will be available  on the WTC Health Program website.

—Alicia Ault (on Twitter @aliciaault)

In the months and years since the attacks of Sept. 11, 2001, the questions have not stopped and the answers have not always been forthcoming. What exactly were the physical and mental effects on those who survived the attacks? What about those who were first responders? Or volunteers who helped clear rubble at the World Trade Center site?

And what has been the impact on people whose family, friends, or co-workers perished on that day in New York, at the Pentagon or in Shanksville, Pa.?

Courtesy Wikimedia Comomns/U.S. Navy/Creative Commons License

On Thursday, Sept. 8, a few days shy of the 10th anniversary of yet another day that will live in infamy, the federal government announced that it was appointing a panel of experts to help advise the WTC Health Program on these issues.

It’s not that they were going entirely unaddressed, but there has been a hodgepodge of efforts, not all of them well-funded or comprehensive. Will this new program with its new slate of scientific advisers be able to provide better answers? Only time will tell.

The WTC Health Program came into existence in July, thanks to the James Zadroga 9/11 Health and Compensation Act of 2010. Named after a police detective who worked at Ground Zero and later died from a respiratory illness in 2006, the bill barely made it into law.

This New York Times article explains some of the back story–Senate Republicans worried that the U.S. would not be able to afford the law’s estimated $7.4 billion cost. That included $3.2 billion over the next 8 years to monitor and treat anyone who worked at the WTC site, and $4.2 billion to the September 11th Victim Compensation Fund.

The Times said that some 60,000 people had already participated in the World Trade Center (WTC) Medical Monitoring and Treatment Program (MMTP). That program was primarily available to response and recovery workers at the WTC site.

The city of New York has been actively monitoring and treating 9-11 survivors. It maintains a detailed list of possible health effects. And most of the MMTP sites were in New York.

The new law goes further, reaching out to others who were at the Pentagon and in Shanksville, and also to residents and workers who were in buildings close to the Twin Towers that day and in the days afterward. The Zadroga Act also puts a higher premium on research and epidemiology.

The 15-member World Trade Center Health Program’s Scientific/Technical Advisory Committee will help shape the research agenda and determine whether more health conditions need to be included in the monitoring and treatment rubric. The panel includes toxicologists, occupational physicians, a pulmonologist, experts in environmental health, a psychiatrist, and two representatives of WTC responders.

The program’s administrator, John Howard, said in the announcement that, “Independent expert scientific advice from the panel will be essential when complex scientific questions arise, and this panel represents the best of the field.”

Howard came under fire in late July when he announced the decision that the program would not pay for cancer-related expenses. That decision may be one of the first to be reviewed by the panel, which will begin meeting in New York in the fall. The advisory committee’s recommendations are just that, apparently. As of now, the program’s administrator has discretion to follow or ignore the panel’s advice.

Once the public meetings begin, the proceedings and recommendations will be available  on the WTC Health Program website.

—Alicia Ault (on Twitter @aliciaault)

Adult smokers in the United States are smoking fewer cigarettes, according to a report released today by the Centers for Disease Control and Prevention.

The proportion of smokers who said they smoked 30 or more cigarettes daily decreased from 12.7% to 8.3%, according to CDC data for 2005-2010. Also, more smokers said they were smoking nine or fewer cigarettes daily, an increase from 16.4% to 21.8%. The number of adult smokers also declined from 20.9% to 19.3%, representing nearly 3 million fewer smokers.

©milosluz/iStockphoto.com

Even as smoking prevalence has decreased overall, the data varies according to race/ethnicity, age, level of education, region, and poverty status (MMWR 2011;60:1-6). Smoking prevalence was lowest among Hispanics (12.5%) and Asians (9.2%), seniors (9.5%), those with a graduate degree (6.3%), and residents of the West (15.9%). The highest prevalence was among American Indians/Alaska Natives (31.4%), adults aged 25-44 years (22%), General Education Development (GED) certificate recipients (45.2%), and residents of the Midwest (21.8%). Categorized by poverty status, 18.3% of those at or above the poverty level smoke, compared with 28.9% of those below the poverty level.

Although smoking appears to be decreasing nationwide, the CDC said the rates have decreased more slowly in the past 5 years. A lack of investment in antismoking campaigns is one of the biggest contributing factors to the slow decline, according to Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health.

"If states were to dedicate more like the 10%-15% that is recommended of these revenues for tobacco control, they’d be fully funding these programs and we’d be seeing a much more rapid decline in tobacco use in our society," Dr. McAfee said during a press briefing. Currently, states are contributing about 2% of their tobacco-related revenues to antismoking efforts.

Dr. McAfee added that states that invest in antismoking programs reap significant health care savings. For example, California has invested about $2.8 billion in antismoking efforts since 1988. During that same period, the state has saved nearly $86 billion in related health care costs and saw adult smoking rates decrease by about 50%, Dr. McAfee said. Smoking costs the United States $193 million annually, nearly equally divided between medical costs and loss of productivity, according to the CDC.

In addition to increased financial support for antismoking initiatives, the CDC recommends that more states place higher taxes on tobacco products and increase smoke-free policies and clinical interventions. As of 2011, 26 states and the District of Columbia have comprehensive smoke-free laws, according to the CDC.

Another 18 states have smoking restrictions at work sites, in restaurants, or in bars. Also, 25 states have added clean air laws that make smoking in public more difficult, Dr. McAfee said.

The report is based on data from the CDC’s 2005-2010 National Health Interview Surveys and the 2010 Behavioral Risk Factor Surveillance System survey. The analysis does not include data for underage smokers.

Adult smokers in the United States are smoking fewer cigarettes, according to a report released today by the Centers for Disease Control and Prevention.

The proportion of smokers who said they smoked 30 or more cigarettes daily decreased from 12.7% to 8.3%, according to CDC data for 2005-2010. Also, more smokers said they were smoking nine or fewer cigarettes daily, an increase from 16.4% to 21.8%. The number of adult smokers also declined from 20.9% to 19.3%, representing nearly 3 million fewer smokers.

©milosluz/iStockphoto.com

Even as smoking prevalence has decreased overall, the data varies according to race/ethnicity, age, level of education, region, and poverty status (MMWR 2011;60:1-6). Smoking prevalence was lowest among Hispanics (12.5%) and Asians (9.2%), seniors (9.5%), those with a graduate degree (6.3%), and residents of the West (15.9%). The highest prevalence was among American Indians/Alaska Natives (31.4%), adults aged 25-44 years (22%), General Education Development (GED) certificate recipients (45.2%), and residents of the Midwest (21.8%). Categorized by poverty status, 18.3% of those at or above the poverty level smoke, compared with 28.9% of those below the poverty level.

Although smoking appears to be decreasing nationwide, the CDC said the rates have decreased more slowly in the past 5 years. A lack of investment in antismoking campaigns is one of the biggest contributing factors to the slow decline, according to Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health.

"If states were to dedicate more like the 10%-15% that is recommended of these revenues for tobacco control, they’d be fully funding these programs and we’d be seeing a much more rapid decline in tobacco use in our society," Dr. McAfee said during a press briefing. Currently, states are contributing about 2% of their tobacco-related revenues to antismoking efforts.

Dr. McAfee added that states that invest in antismoking programs reap significant health care savings. For example, California has invested about $2.8 billion in antismoking efforts since 1988. During that same period, the state has saved nearly $86 billion in related health care costs and saw adult smoking rates decrease by about 50%, Dr. McAfee said. Smoking costs the United States $193 million annually, nearly equally divided between medical costs and loss of productivity, according to the CDC.

In addition to increased financial support for antismoking initiatives, the CDC recommends that more states place higher taxes on tobacco products and increase smoke-free policies and clinical interventions. As of 2011, 26 states and the District of Columbia have comprehensive smoke-free laws, according to the CDC.

Another 18 states have smoking restrictions at work sites, in restaurants, or in bars. Also, 25 states have added clean air laws that make smoking in public more difficult, Dr. McAfee said.

The report is based on data from the CDC’s 2005-2010 National Health Interview Surveys and the 2010 Behavioral Risk Factor Surveillance System survey. The analysis does not include data for underage smokers.

Adult smokers in the United States are smoking fewer cigarettes, according to a report released today by the Centers for Disease Control and Prevention.

The proportion of smokers who said they smoked 30 or more cigarettes daily decreased from 12.7% to 8.3%, according to CDC data for 2005-2010. Also, more smokers said they were smoking nine or fewer cigarettes daily, an increase from 16.4% to 21.8%. The number of adult smokers also declined from 20.9% to 19.3%, representing nearly 3 million fewer smokers.

©milosluz/iStockphoto.com

Even as smoking prevalence has decreased overall, the data varies according to race/ethnicity, age, level of education, region, and poverty status (MMWR 2011;60:1-6). Smoking prevalence was lowest among Hispanics (12.5%) and Asians (9.2%), seniors (9.5%), those with a graduate degree (6.3%), and residents of the West (15.9%). The highest prevalence was among American Indians/Alaska Natives (31.4%), adults aged 25-44 years (22%), General Education Development (GED) certificate recipients (45.2%), and residents of the Midwest (21.8%). Categorized by poverty status, 18.3% of those at or above the poverty level smoke, compared with 28.9% of those below the poverty level.

Although smoking appears to be decreasing nationwide, the CDC said the rates have decreased more slowly in the past 5 years. A lack of investment in antismoking campaigns is one of the biggest contributing factors to the slow decline, according to Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health.

"If states were to dedicate more like the 10%-15% that is recommended of these revenues for tobacco control, they’d be fully funding these programs and we’d be seeing a much more rapid decline in tobacco use in our society," Dr. McAfee said during a press briefing. Currently, states are contributing about 2% of their tobacco-related revenues to antismoking efforts.

Dr. McAfee added that states that invest in antismoking programs reap significant health care savings. For example, California has invested about $2.8 billion in antismoking efforts since 1988. During that same period, the state has saved nearly $86 billion in related health care costs and saw adult smoking rates decrease by about 50%, Dr. McAfee said. Smoking costs the United States $193 million annually, nearly equally divided between medical costs and loss of productivity, according to the CDC.

In addition to increased financial support for antismoking initiatives, the CDC recommends that more states place higher taxes on tobacco products and increase smoke-free policies and clinical interventions. As of 2011, 26 states and the District of Columbia have comprehensive smoke-free laws, according to the CDC.

Another 18 states have smoking restrictions at work sites, in restaurants, or in bars. Also, 25 states have added clean air laws that make smoking in public more difficult, Dr. McAfee said.

The report is based on data from the CDC’s 2005-2010 National Health Interview Surveys and the 2010 Behavioral Risk Factor Surveillance System survey. The analysis does not include data for underage smokers.