Pulmonary Health Hub

Dr. Nancy Ostrom discusses the EIB Landmark Survey's findings regarding the impact that exercise-related respiratory symptoms have on people with asthma.

Dr. Nancy Ostrom discusses the EIB Landmark Survey's findings regarding the impact that exercise-related respiratory symptoms have on people with asthma.

Dr. Nancy Ostrom discusses the EIB Landmark Survey's findings regarding the impact that exercise-related respiratory symptoms have on people with asthma.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.

The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.

The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.

A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.

The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.

Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).

When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.

"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.

Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.

The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.

Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.

The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.

Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.

This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.

"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.

Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Doubling, quadrupling, or octupling the maintenance dose of inhaled corticosteroids in the early course of an asthma exacerbation did not result in significant differences in symptoms or in the use of oral corticosteroids, results from a randomized controlled study demonstrated.

"If you strongly feel that the patient is deteriorating, you can use clinical judgment and give them an oral corticosteroid; but don’t increase the inhaled corticosteroid dose – it’s not going to make a difference," Dr. Ejaz Yousef said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Increasing the dose of inhaled corticosteroid has some consequences. It can suppress the hypothalamic-pituitary adrenal axis, for example."

As an alternative to oral corticosteroids for the management of asthma exacerbations, the 1997 National Asthma Education and Prevention Program recommended doubling the maintenance dose of inhaled corticosteroids. However, Dr. Yousef said that at least two published studies found no significant improvement in patients treated with twice the inhaled corticosteroid dose, compared with placebo (Thorax 2004;59;550-6 and Lancet 2004;363:271-5). It remains unknown what kind of impact even larger doses would have on the need for oral corticosteroids.

To find out, Dr. Yousef, chief of the division of pediatric allergy/immunology at Nemours Children’s Clinic, Wilmington, Del., and his associates collected data on 197 children aged 2-17 years who had been maintained on inhaled corticosteroids for at least 90 days.

The children were randomly assigned to one of three 12-day treatment protocols to be implemented if they developed an exacerbation of their asthma symptoms: twice their maintenance dose, four times their maintenance dose, or eight times their maintenance dose. Physicians assessed the children’s clinical status with symptom scores via telephone calls or clinic visits following initiation of therapy protocol.

The researchers excluded children who had chronic, unstable asthma, those who had lung pathology as well as asthma, and those who had additional medical conditions or a history of smoking or substance abuse. An increase in symptoms was defined as a decrease in peak flow values of 50%-80% of the patient’s best and/or increased cough and/or wheezing present for 24-72 hours responsive to beta-agonist therapy. Patients were required to report symptoms within 72 hours of onset.

Symptom scores were obtained via telephone on day 3, 7, and 14 of the treatment plan and included the presence and severity of day and nighttime cough and wheeze, shortness of breath, and exercise intolerance. Scores ranged from 0 to 4 for each symptom, with 0 meaning none and 4 meaning severe.

The primary outcome was the frequency of need to progress to therapy with systemic corticosteroids.

Of the 197 patients, 82 completed the increased dosing protocol, and their mean age was 6 years. Among those 82 patients, only four required treatment with systemic corticosteroids: two from the double maintenance dose group and two from the quadruple maintenance dose group.

Dr. Yousef reported that there was no significant difference in mean symptom scores among the three groups at baseline or at days 3, 7, and 14. In all groups, the scores improved over the course of treatment regardless of the dosage of inhaled corticosteroids administered. There was no significant difference in the time from onset of symptoms to the initiation of the study protocol in the three groups and no difference between patients who did and did not require treatment with systemic corticosteroids.

The results suggest "that it was not the medication alone that improved the outcome," the researchers wrote in their abstract. "It is possible that placebo effect of administering a medication, close contact with a supervising physician, and contact early in the course of an exacerbation played a significant role in obtaining this outcome."

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

SAN FRANCISCO – Lung function alone is a poor marker of asthma control in children, results from a large retrospective analysis demonstrated.

"Physicians should use all components of the 2007 National Asthma Education and Prevention Program Expert Report 3 guidelines, asking questions to patients not only about daytime and nighttime symptoms, but doing lung function testing as well," Dr. Edward K. Hu advised during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Even [among] those patients who are enrolled in a disease management program, there is still going to be a large minority who are going to be uncontrolled in one way or another, despite follow-up visits and seeing asthma specialists."

Dr. Hu, a fellow in the division of allergy and immunology at the Los Angeles County/University of Southern California Medical Center, Los Angeles, and his associates studied 453 children aged 5-18 years who were enrolled in an asthma management program in Los Angeles County in 2009 and who made a total of 886 follow-up visits. Initial analysis defined asthma control based solely on lung function. Secondary analysis included all components of asthma control based on the 2007 National Asthma Education and Prevention Program Expert Report 3, which included impairment and risk. Of the 453 children, 61% were male and 83% were Hispanic.

At baseline more than one-quarter of patients (29%) had intermittent disease, 21% had mild persistent disease, 25% had moderate persistent disease, and 25% had severe persistent disease.

Dr. Hu reported that when lung function alone was used, 17% of children exhibited asthma that was not well controlled, and 5% exhibited asthma that was poorly controlled. Inclusion of impairment and risk resulted in a downgrade of asthma control in an additional 22% of children.

The researchers also found that males, aged 8-11 years, were significantly more likely than their female counterparts to present with normal lung function and uncontrolled disease due to other factors (24% vs. 15%).

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

SAN FRANCISCO – Lung function alone is a poor marker of asthma control in children, results from a large retrospective analysis demonstrated.

"Physicians should use all components of the 2007 National Asthma Education and Prevention Program Expert Report 3 guidelines, asking questions to patients not only about daytime and nighttime symptoms, but doing lung function testing as well," Dr. Edward K. Hu advised during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Even [among] those patients who are enrolled in a disease management program, there is still going to be a large minority who are going to be uncontrolled in one way or another, despite follow-up visits and seeing asthma specialists."

Dr. Hu, a fellow in the division of allergy and immunology at the Los Angeles County/University of Southern California Medical Center, Los Angeles, and his associates studied 453 children aged 5-18 years who were enrolled in an asthma management program in Los Angeles County in 2009 and who made a total of 886 follow-up visits. Initial analysis defined asthma control based solely on lung function. Secondary analysis included all components of asthma control based on the 2007 National Asthma Education and Prevention Program Expert Report 3, which included impairment and risk. Of the 453 children, 61% were male and 83% were Hispanic.

At baseline more than one-quarter of patients (29%) had intermittent disease, 21% had mild persistent disease, 25% had moderate persistent disease, and 25% had severe persistent disease.

Dr. Hu reported that when lung function alone was used, 17% of children exhibited asthma that was not well controlled, and 5% exhibited asthma that was poorly controlled. Inclusion of impairment and risk resulted in a downgrade of asthma control in an additional 22% of children.

The researchers also found that males, aged 8-11 years, were significantly more likely than their female counterparts to present with normal lung function and uncontrolled disease due to other factors (24% vs. 15%).

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

SAN FRANCISCO – Lung function alone is a poor marker of asthma control in children, results from a large retrospective analysis demonstrated.

"Physicians should use all components of the 2007 National Asthma Education and Prevention Program Expert Report 3 guidelines, asking questions to patients not only about daytime and nighttime symptoms, but doing lung function testing as well," Dr. Edward K. Hu advised during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. "Even [among] those patients who are enrolled in a disease management program, there is still going to be a large minority who are going to be uncontrolled in one way or another, despite follow-up visits and seeing asthma specialists."

Dr. Hu, a fellow in the division of allergy and immunology at the Los Angeles County/University of Southern California Medical Center, Los Angeles, and his associates studied 453 children aged 5-18 years who were enrolled in an asthma management program in Los Angeles County in 2009 and who made a total of 886 follow-up visits. Initial analysis defined asthma control based solely on lung function. Secondary analysis included all components of asthma control based on the 2007 National Asthma Education and Prevention Program Expert Report 3, which included impairment and risk. Of the 453 children, 61% were male and 83% were Hispanic.

At baseline more than one-quarter of patients (29%) had intermittent disease, 21% had mild persistent disease, 25% had moderate persistent disease, and 25% had severe persistent disease.

Dr. Hu reported that when lung function alone was used, 17% of children exhibited asthma that was not well controlled, and 5% exhibited asthma that was poorly controlled. Inclusion of impairment and risk resulted in a downgrade of asthma control in an additional 22% of children.

The researchers also found that males, aged 8-11 years, were significantly more likely than their female counterparts to present with normal lung function and uncontrolled disease due to other factors (24% vs. 15%).

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

ORLANDO – Although the mean increase in body weight was "impressive," ghrelin treatment failed to improve functional outcomes for patients with cachexia associated with chronic obstructive pulmonary disease in a phase II trial.

Although this exploratory trial revealed that ghrelin use caused gains in lean muscle mass and function in COPD patients with severe cachexia, improvements in patient function were "rather disappointing," Dr. Joseph M. Gertner said at an international symposium on IGF-1, GH, and Gherlin/GHS.

Improvement in patient function was a study end point stipulated by the Food and Drug Administration for the preclinical trials of ghrelin agent SUN11031 (Asubio Pharmaceuticals).

"If the only thing you think you need to do to correct cachexia is increase body weight, then this trial worked just fine," said Dr. Gertner, vice president of medical affairs at Asubio. The study showed a 2.5-kg mean weight gain in the high-dose group (40 mcg/kg twice daily) and a 1.5-kg gain in the low-dose group (20 mcg/kg twice daily) at 12 weeks, he said.

"The secondary end point, mean change in baseline body weight, was impressive," Dr. Gertner said at the meeting, sponsored by the University of South Florida, Tampa.

The 214 patients with COPD and cachexia in the intent-to-treat analysis included 73 patients randomized to receive the low dose of ghrelin, 69 to the high dose, and 72 to placebo. Patients were aged 50 years or older (average, 65 years).

The primary end point was performance on a 6-minute walk test, which is widely used to assess physical performance in COPD. Dr. Gertner and his associates also used the short physical performance battery (SPPB), a validated measure that is predictive of morbidity and mortality. The SPPB has three components: a balance test ("no influence in our study"), a chair stand (number of times a patient can stand from a sitting position in 5 or 10 seconds), and a gait speed test (time to walk 4 m).

Handgrip strength, maximum inspiratory pressure, and changes in body weight, body composition, and appetite were also assessed.

"No evidence of strength or functional improvement was observed in the [intent-to-treat] population," Dr. Gertner said. For example, the low-dose group fared significantly worse on the 6-minute walk test than did the placebo group, and no significant improvements on the SPPB test were seen, he said.

Cachexia was defined as a body mass index of 21 kg/m² or less for men and 20 or less for women, or documented involuntary weight loss of more than 5% over 12 months.

More advanced cachexia was defined as a BMI of less than 16 for men or less than 15 for women.

Among those in the subgroup with more advanced cachexia, significant improvements on the 6-minute walk and SPPB tests were seen with high-dose ghrelin, and positive trends on these tests were found with low-dose ghrelin. In addition, "more than 80% of these very severely cachectic patients increased their lean body mass," Dr. Gertner said.

Ghrelin is a logical choice to combat cachexia, Dr. Gertner said, because "the properties of this hormone seem to line up well with pathophysiologic properties of cachexia." For example, ghrelin causes the release of growth hormone, which might counter catabolism. Ghrelin also increases appetite, improves metabolic rate (thereby improving efficiency of food conversion to body mass), and stimulates gastrointestinal motility. "With all these properties of one ligand, it is not surprising many companies have tried to use ghrelin and the ghrelin secretagogues to reverse cachexia."

Dr. Gertner and his coauthors are full-time employees of Asubio Pharmaceuticals.

ORLANDO – Although the mean increase in body weight was "impressive," ghrelin treatment failed to improve functional outcomes for patients with cachexia associated with chronic obstructive pulmonary disease in a phase II trial.

Although this exploratory trial revealed that ghrelin use caused gains in lean muscle mass and function in COPD patients with severe cachexia, improvements in patient function were "rather disappointing," Dr. Joseph M. Gertner said at an international symposium on IGF-1, GH, and Gherlin/GHS.

Improvement in patient function was a study end point stipulated by the Food and Drug Administration for the preclinical trials of ghrelin agent SUN11031 (Asubio Pharmaceuticals).

"If the only thing you think you need to do to correct cachexia is increase body weight, then this trial worked just fine," said Dr. Gertner, vice president of medical affairs at Asubio. The study showed a 2.5-kg mean weight gain in the high-dose group (40 mcg/kg twice daily) and a 1.5-kg gain in the low-dose group (20 mcg/kg twice daily) at 12 weeks, he said.

"The secondary end point, mean change in baseline body weight, was impressive," Dr. Gertner said at the meeting, sponsored by the University of South Florida, Tampa.

The 214 patients with COPD and cachexia in the intent-to-treat analysis included 73 patients randomized to receive the low dose of ghrelin, 69 to the high dose, and 72 to placebo. Patients were aged 50 years or older (average, 65 years).

The primary end point was performance on a 6-minute walk test, which is widely used to assess physical performance in COPD. Dr. Gertner and his associates also used the short physical performance battery (SPPB), a validated measure that is predictive of morbidity and mortality. The SPPB has three components: a balance test ("no influence in our study"), a chair stand (number of times a patient can stand from a sitting position in 5 or 10 seconds), and a gait speed test (time to walk 4 m).

Handgrip strength, maximum inspiratory pressure, and changes in body weight, body composition, and appetite were also assessed.

"No evidence of strength or functional improvement was observed in the [intent-to-treat] population," Dr. Gertner said. For example, the low-dose group fared significantly worse on the 6-minute walk test than did the placebo group, and no significant improvements on the SPPB test were seen, he said.

Cachexia was defined as a body mass index of 21 kg/m² or less for men and 20 or less for women, or documented involuntary weight loss of more than 5% over 12 months.

More advanced cachexia was defined as a BMI of less than 16 for men or less than 15 for women.

Among those in the subgroup with more advanced cachexia, significant improvements on the 6-minute walk and SPPB tests were seen with high-dose ghrelin, and positive trends on these tests were found with low-dose ghrelin. In addition, "more than 80% of these very severely cachectic patients increased their lean body mass," Dr. Gertner said.

Ghrelin is a logical choice to combat cachexia, Dr. Gertner said, because "the properties of this hormone seem to line up well with pathophysiologic properties of cachexia." For example, ghrelin causes the release of growth hormone, which might counter catabolism. Ghrelin also increases appetite, improves metabolic rate (thereby improving efficiency of food conversion to body mass), and stimulates gastrointestinal motility. "With all these properties of one ligand, it is not surprising many companies have tried to use ghrelin and the ghrelin secretagogues to reverse cachexia."

Dr. Gertner and his coauthors are full-time employees of Asubio Pharmaceuticals.

ORLANDO – Although the mean increase in body weight was "impressive," ghrelin treatment failed to improve functional outcomes for patients with cachexia associated with chronic obstructive pulmonary disease in a phase II trial.

Although this exploratory trial revealed that ghrelin use caused gains in lean muscle mass and function in COPD patients with severe cachexia, improvements in patient function were "rather disappointing," Dr. Joseph M. Gertner said at an international symposium on IGF-1, GH, and Gherlin/GHS.

Improvement in patient function was a study end point stipulated by the Food and Drug Administration for the preclinical trials of ghrelin agent SUN11031 (Asubio Pharmaceuticals).

"If the only thing you think you need to do to correct cachexia is increase body weight, then this trial worked just fine," said Dr. Gertner, vice president of medical affairs at Asubio. The study showed a 2.5-kg mean weight gain in the high-dose group (40 mcg/kg twice daily) and a 1.5-kg gain in the low-dose group (20 mcg/kg twice daily) at 12 weeks, he said.

"The secondary end point, mean change in baseline body weight, was impressive," Dr. Gertner said at the meeting, sponsored by the University of South Florida, Tampa.

The 214 patients with COPD and cachexia in the intent-to-treat analysis included 73 patients randomized to receive the low dose of ghrelin, 69 to the high dose, and 72 to placebo. Patients were aged 50 years or older (average, 65 years).

The primary end point was performance on a 6-minute walk test, which is widely used to assess physical performance in COPD. Dr. Gertner and his associates also used the short physical performance battery (SPPB), a validated measure that is predictive of morbidity and mortality. The SPPB has three components: a balance test ("no influence in our study"), a chair stand (number of times a patient can stand from a sitting position in 5 or 10 seconds), and a gait speed test (time to walk 4 m).

Handgrip strength, maximum inspiratory pressure, and changes in body weight, body composition, and appetite were also assessed.

"No evidence of strength or functional improvement was observed in the [intent-to-treat] population," Dr. Gertner said. For example, the low-dose group fared significantly worse on the 6-minute walk test than did the placebo group, and no significant improvements on the SPPB test were seen, he said.

Cachexia was defined as a body mass index of 21 kg/m² or less for men and 20 or less for women, or documented involuntary weight loss of more than 5% over 12 months.

More advanced cachexia was defined as a BMI of less than 16 for men or less than 15 for women.

Among those in the subgroup with more advanced cachexia, significant improvements on the 6-minute walk and SPPB tests were seen with high-dose ghrelin, and positive trends on these tests were found with low-dose ghrelin. In addition, "more than 80% of these very severely cachectic patients increased their lean body mass," Dr. Gertner said.

Ghrelin is a logical choice to combat cachexia, Dr. Gertner said, because "the properties of this hormone seem to line up well with pathophysiologic properties of cachexia." For example, ghrelin causes the release of growth hormone, which might counter catabolism. Ghrelin also increases appetite, improves metabolic rate (thereby improving efficiency of food conversion to body mass), and stimulates gastrointestinal motility. "With all these properties of one ligand, it is not surprising many companies have tried to use ghrelin and the ghrelin secretagogues to reverse cachexia."

Dr. Gertner and his coauthors are full-time employees of Asubio Pharmaceuticals.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.