Patrice Wendling

MONTREAL — Adenosine stress testing with supplemental arm pumping exercise had the same diagnostic accuracy as exercise stress testing in detecting significant coronary artery disease in a study of 302 patients.

The results validate a long-standing practice at Massachusetts General Hospital, Boston, where supplemental arm exercise with light weights—not arm exercise with squeeze balls and not a treadmill walk—has been used for a decade to prevent adenosine-related side effects during myocardial perfusion imaging.

Arm-pumping exercise is utilized in all patients who are unable to safely negotiate a treadmill, which includes many inpatients as well as elderly and arthritic patients and those with increased risk of falling because of seizure or balance disorders, Dr. Arash Kardan, of the hospital, said in an interview at the annual meeting of the American Society of Nuclear Cardiology.

Though not well studied or understood, supplemental exercise is thought to mitigate adenosine-related bradycardia and hypotension via a neurocirculatory response, he said. “It really works; it's not just a distraction for the patient.”

The study was presented in a poster at the meeting, and included 302 patients referred for clinically indicated rest-stress myocardial perfusion imaging (MPI) with technetium 99m sestamibi. Patients underwent either exercise stress testing using the standard Bruce protocol achieving 85% of maximum predicted heart rate, or received an adenosine infusion of 0.14 mg/kg per minute for 4–5 minutes in one arm and pumped a 2.5-pound weight with their opposite arm.

All patients underwent coronary angiography within 2 months of MPI. Positive MPI was defined as demonstrating a reversible defect, while positive angiography was defined as the presence of any lesion with greater than 50% stenosis. Patients with a past history of myocardial infarction or coronary bypass surgery were included for analysis. Overall, one-third of patients had prior reported coronary artery disease.

There were 158 patients in the exercise stress group, with a mean age of 63 years. The sensitivity was 91% and specificity 100%, the authors reported.

There were 144 patients in the arm exercise group, with a mean age of 68 years. Sensitivity was 84% and specificity 81%; the differences from the exercise stress group were nonsignificant. No adenosine arm tests required termination because of side effects. All exercise treadmill tests were completed as well, he said.

The hospital has performed 10,000 adenosine tests using the arm-pumping exercises, and less than 1% of tests have been terminated, Dr. Kardan said. “We've been doing this for years, and wanted to get the message out.”

MONTREAL — Adenosine stress testing with supplemental arm pumping exercise had the same diagnostic accuracy as exercise stress testing in detecting significant coronary artery disease in a study of 302 patients.

The results validate a long-standing practice at Massachusetts General Hospital, Boston, where supplemental arm exercise with light weights—not arm exercise with squeeze balls and not a treadmill walk—has been used for a decade to prevent adenosine-related side effects during myocardial perfusion imaging.

Arm-pumping exercise is utilized in all patients who are unable to safely negotiate a treadmill, which includes many inpatients as well as elderly and arthritic patients and those with increased risk of falling because of seizure or balance disorders, Dr. Arash Kardan, of the hospital, said in an interview at the annual meeting of the American Society of Nuclear Cardiology.

Though not well studied or understood, supplemental exercise is thought to mitigate adenosine-related bradycardia and hypotension via a neurocirculatory response, he said. “It really works; it's not just a distraction for the patient.”

The study was presented in a poster at the meeting, and included 302 patients referred for clinically indicated rest-stress myocardial perfusion imaging (MPI) with technetium 99m sestamibi. Patients underwent either exercise stress testing using the standard Bruce protocol achieving 85% of maximum predicted heart rate, or received an adenosine infusion of 0.14 mg/kg per minute for 4–5 minutes in one arm and pumped a 2.5-pound weight with their opposite arm.

All patients underwent coronary angiography within 2 months of MPI. Positive MPI was defined as demonstrating a reversible defect, while positive angiography was defined as the presence of any lesion with greater than 50% stenosis. Patients with a past history of myocardial infarction or coronary bypass surgery were included for analysis. Overall, one-third of patients had prior reported coronary artery disease.

There were 158 patients in the exercise stress group, with a mean age of 63 years. The sensitivity was 91% and specificity 100%, the authors reported.

There were 144 patients in the arm exercise group, with a mean age of 68 years. Sensitivity was 84% and specificity 81%; the differences from the exercise stress group were nonsignificant. No adenosine arm tests required termination because of side effects. All exercise treadmill tests were completed as well, he said.

The hospital has performed 10,000 adenosine tests using the arm-pumping exercises, and less than 1% of tests have been terminated, Dr. Kardan said. “We've been doing this for years, and wanted to get the message out.”

MONTREAL — Adenosine stress testing with supplemental arm pumping exercise had the same diagnostic accuracy as exercise stress testing in detecting significant coronary artery disease in a study of 302 patients.

The results validate a long-standing practice at Massachusetts General Hospital, Boston, where supplemental arm exercise with light weights—not arm exercise with squeeze balls and not a treadmill walk—has been used for a decade to prevent adenosine-related side effects during myocardial perfusion imaging.

Arm-pumping exercise is utilized in all patients who are unable to safely negotiate a treadmill, which includes many inpatients as well as elderly and arthritic patients and those with increased risk of falling because of seizure or balance disorders, Dr. Arash Kardan, of the hospital, said in an interview at the annual meeting of the American Society of Nuclear Cardiology.

Though not well studied or understood, supplemental exercise is thought to mitigate adenosine-related bradycardia and hypotension via a neurocirculatory response, he said. “It really works; it's not just a distraction for the patient.”

The study was presented in a poster at the meeting, and included 302 patients referred for clinically indicated rest-stress myocardial perfusion imaging (MPI) with technetium 99m sestamibi. Patients underwent either exercise stress testing using the standard Bruce protocol achieving 85% of maximum predicted heart rate, or received an adenosine infusion of 0.14 mg/kg per minute for 4–5 minutes in one arm and pumped a 2.5-pound weight with their opposite arm.

All patients underwent coronary angiography within 2 months of MPI. Positive MPI was defined as demonstrating a reversible defect, while positive angiography was defined as the presence of any lesion with greater than 50% stenosis. Patients with a past history of myocardial infarction or coronary bypass surgery were included for analysis. Overall, one-third of patients had prior reported coronary artery disease.

There were 158 patients in the exercise stress group, with a mean age of 63 years. The sensitivity was 91% and specificity 100%, the authors reported.

There were 144 patients in the arm exercise group, with a mean age of 68 years. Sensitivity was 84% and specificity 81%; the differences from the exercise stress group were nonsignificant. No adenosine arm tests required termination because of side effects. All exercise treadmill tests were completed as well, he said.

The hospital has performed 10,000 adenosine tests using the arm-pumping exercises, and less than 1% of tests have been terminated, Dr. Kardan said. “We've been doing this for years, and wanted to get the message out.”

MONTREAL — When treating habit cough, one should avoid steroids and consider potential psychological stressors, Dr. Louis Landau said at the Seventh International Congress on Pediatric Pulmonology.

Habit cough is a rare diagnosis in adults, but studies suggest it is made in 3%–10% of children with cough of unknown origin that persists for more than 1 month. It frequently results in extended school absences and multiple therapeutic trials, including high-dose steroids.

It is not the typical cough seen in children, and is often described as sounding like the honk of a Canada goose.

“It's a very loud, dry bark,” said Dr. Landau, emeritus professor and former dean, faculty of medicine and dentistry, University of Western Australia in Crawley.

Although this bizarre sound is alarming to those around the coughing child, the child is generally not perturbed by it.

Another clinical feature is that it is the only type of cough that goes away when the child sleeps, he said.

Dr. Landau said there often is evidence of stress in these patients, but that is not to suggest they have major psychological problems. They are frequently high-achieving children under a lot of pressure to perform either in school or sports.

The typical duration of a habit cough is difficult to define because diagnosis frequently is made after several referrals, making the origin of the cough difficult to pinpoint. The literature is not consistent in its definition of habit cough, and most studies haven't differentiated among habit coughs, tics, and Tourette's syndrome.

On rare occasions, habit cough may be a manifestation of a tic disorder or symptom of Tourette's syndrome, but it is uncommon, Dr. Landau said.

The American College of Chest Physicians recently published evidence-based clinical practice guidelines for habit cough, tic cough, and psychogenic cough in adult and pediatric populations (Chest 2006;129:174S-9S).

The good news, Dr. Landau explained, is that treatment is very effective after the diagnosis is made and explained to the parents. Habit cough is generally managed by exclusion of organic disease, reassurance, addressing any identified stressors, and breathing-control exercises, he added.

Habit cough is often evidence of stress. It is often present in high-achieving children who are under a lot of pressure. DR. LANDAU

MONTREAL — When treating habit cough, one should avoid steroids and consider potential psychological stressors, Dr. Louis Landau said at the Seventh International Congress on Pediatric Pulmonology.

Habit cough is a rare diagnosis in adults, but studies suggest it is made in 3%–10% of children with cough of unknown origin that persists for more than 1 month. It frequently results in extended school absences and multiple therapeutic trials, including high-dose steroids.

It is not the typical cough seen in children, and is often described as sounding like the honk of a Canada goose.

“It's a very loud, dry bark,” said Dr. Landau, emeritus professor and former dean, faculty of medicine and dentistry, University of Western Australia in Crawley.

Although this bizarre sound is alarming to those around the coughing child, the child is generally not perturbed by it.

Another clinical feature is that it is the only type of cough that goes away when the child sleeps, he said.

Dr. Landau said there often is evidence of stress in these patients, but that is not to suggest they have major psychological problems. They are frequently high-achieving children under a lot of pressure to perform either in school or sports.

The typical duration of a habit cough is difficult to define because diagnosis frequently is made after several referrals, making the origin of the cough difficult to pinpoint. The literature is not consistent in its definition of habit cough, and most studies haven't differentiated among habit coughs, tics, and Tourette's syndrome.

On rare occasions, habit cough may be a manifestation of a tic disorder or symptom of Tourette's syndrome, but it is uncommon, Dr. Landau said.

The American College of Chest Physicians recently published evidence-based clinical practice guidelines for habit cough, tic cough, and psychogenic cough in adult and pediatric populations (Chest 2006;129:174S-9S).

The good news, Dr. Landau explained, is that treatment is very effective after the diagnosis is made and explained to the parents. Habit cough is generally managed by exclusion of organic disease, reassurance, addressing any identified stressors, and breathing-control exercises, he added.

Habit cough is often evidence of stress. It is often present in high-achieving children who are under a lot of pressure. DR. LANDAU

MONTREAL — When treating habit cough, one should avoid steroids and consider potential psychological stressors, Dr. Louis Landau said at the Seventh International Congress on Pediatric Pulmonology.

Habit cough is a rare diagnosis in adults, but studies suggest it is made in 3%–10% of children with cough of unknown origin that persists for more than 1 month. It frequently results in extended school absences and multiple therapeutic trials, including high-dose steroids.

It is not the typical cough seen in children, and is often described as sounding like the honk of a Canada goose.

“It's a very loud, dry bark,” said Dr. Landau, emeritus professor and former dean, faculty of medicine and dentistry, University of Western Australia in Crawley.

Although this bizarre sound is alarming to those around the coughing child, the child is generally not perturbed by it.

Another clinical feature is that it is the only type of cough that goes away when the child sleeps, he said.

Dr. Landau said there often is evidence of stress in these patients, but that is not to suggest they have major psychological problems. They are frequently high-achieving children under a lot of pressure to perform either in school or sports.

The typical duration of a habit cough is difficult to define because diagnosis frequently is made after several referrals, making the origin of the cough difficult to pinpoint. The literature is not consistent in its definition of habit cough, and most studies haven't differentiated among habit coughs, tics, and Tourette's syndrome.

On rare occasions, habit cough may be a manifestation of a tic disorder or symptom of Tourette's syndrome, but it is uncommon, Dr. Landau said.

The American College of Chest Physicians recently published evidence-based clinical practice guidelines for habit cough, tic cough, and psychogenic cough in adult and pediatric populations (Chest 2006;129:174S-9S).

The good news, Dr. Landau explained, is that treatment is very effective after the diagnosis is made and explained to the parents. Habit cough is generally managed by exclusion of organic disease, reassurance, addressing any identified stressors, and breathing-control exercises, he added.

Habit cough is often evidence of stress. It is often present in high-achieving children who are under a lot of pressure. DR. LANDAU

MONTREAL — There is a disconnect in communications between physicians and parents of children with asthma, according to an analysis of data from a new global asthma survey.

Parents and physicians disagree on the amount of time dedicated to asthma education in the office; who initiates discussion about medication side effects; and the level of treatment compliance with asthma medication.

The North American pediatric findings of the Global Asthma Physician and Patient (GAPP) study also confirm what most physicians already know: Asthma medication compliance is low; patients with poor compliance experience more symptoms; and side effects lead patients to switch or drop medications.

The authors conclude that patient compliance and outcomes could be enhanced through better physician-patient communications and asthma education, and the availability of new treatment options with lower side-effect profiles, Dr. Ronald Dahl of Aarhus (Denmark) University Hospital, and his associates on the GAPP Survey Working Group reported in a poster at the Seventh International Congress on Pediatric Pulmonology.

The survey was conducted between May and August 2005 in 16 countries and included a total of 5,482 online and telephone interviews with 1,017 parents of children diagnosed with asthma, 1,006 physicians who treat children with asthma, 1,726 adults over 18 years of age with asthma, and 1,733 physicians who treat adults. It was supported by an educational grant from Altana Pharma and conducted in cooperation with the World Allergy Organization and American College of Allergy, Asthma, and Immunology. It was sufficiently powered to ensure statistical significance globally and in each country.

The analysis presented here was based on 618 interviews conducted in North America among 314 parents and 304 physicians.

Among parents interviewed, 62% reported their children's asthma as mild; 33% as moderate; and 5% as severe. In the 12 months before the interview, parents reported a number of events demonstrating poor asthma control such as making an unscheduled visit to their doctor (34%), going to the emergency department (11%), and admission to the hospital (5%).

According to parents, physicians don't discuss specific asthma management issues such as development of an individual management plan (66%); correct inhaler technique (69%); and keeping daily symptom or medication diaries (25%). Physicians' perceptions of the incidence of these exchanges were 90%, 97%, 53%, respectively.

Parents also perceive that less time is spent on asthma education than physicians perceive. Whereas 18% of parents reported that during a typical office visit, no time is spent on asthma education, about 84% of physicians report spending at least half of their office time on education.

Overall, 27% of parents answered “false” or “not sure” when asked whether mild asthma attacks could be fatal, which demonstrates a general lack of understanding about the disease, the authors reported. Global findings from the survey indicate that treatment compliance increased with the level of asthma education, a trend that also was seen in local results.

Of those patients with asthma who take or had taken asthma medication, 37% of parents reported never discussing short-term side effects such as fungal infection, sore throat, or hoarseness with their physicians; and 55% reported never discussing long-term effects including weight gain, weakening of the bones or changing bone density. This compares with physician reports of 1% and 6%, respectively. When asked who typically brings up the topic of asthma medication side effects, 62% of parents said they or their child did; 76% of physicians said they did.

For more information on the study findings, go to www.gappsurvey.org

MONTREAL — There is a disconnect in communications between physicians and parents of children with asthma, according to an analysis of data from a new global asthma survey.

Parents and physicians disagree on the amount of time dedicated to asthma education in the office; who initiates discussion about medication side effects; and the level of treatment compliance with asthma medication.

The North American pediatric findings of the Global Asthma Physician and Patient (GAPP) study also confirm what most physicians already know: Asthma medication compliance is low; patients with poor compliance experience more symptoms; and side effects lead patients to switch or drop medications.

The authors conclude that patient compliance and outcomes could be enhanced through better physician-patient communications and asthma education, and the availability of new treatment options with lower side-effect profiles, Dr. Ronald Dahl of Aarhus (Denmark) University Hospital, and his associates on the GAPP Survey Working Group reported in a poster at the Seventh International Congress on Pediatric Pulmonology.

The survey was conducted between May and August 2005 in 16 countries and included a total of 5,482 online and telephone interviews with 1,017 parents of children diagnosed with asthma, 1,006 physicians who treat children with asthma, 1,726 adults over 18 years of age with asthma, and 1,733 physicians who treat adults. It was supported by an educational grant from Altana Pharma and conducted in cooperation with the World Allergy Organization and American College of Allergy, Asthma, and Immunology. It was sufficiently powered to ensure statistical significance globally and in each country.

The analysis presented here was based on 618 interviews conducted in North America among 314 parents and 304 physicians.

Among parents interviewed, 62% reported their children's asthma as mild; 33% as moderate; and 5% as severe. In the 12 months before the interview, parents reported a number of events demonstrating poor asthma control such as making an unscheduled visit to their doctor (34%), going to the emergency department (11%), and admission to the hospital (5%).

According to parents, physicians don't discuss specific asthma management issues such as development of an individual management plan (66%); correct inhaler technique (69%); and keeping daily symptom or medication diaries (25%). Physicians' perceptions of the incidence of these exchanges were 90%, 97%, 53%, respectively.

Parents also perceive that less time is spent on asthma education than physicians perceive. Whereas 18% of parents reported that during a typical office visit, no time is spent on asthma education, about 84% of physicians report spending at least half of their office time on education.

Overall, 27% of parents answered “false” or “not sure” when asked whether mild asthma attacks could be fatal, which demonstrates a general lack of understanding about the disease, the authors reported. Global findings from the survey indicate that treatment compliance increased with the level of asthma education, a trend that also was seen in local results.

Of those patients with asthma who take or had taken asthma medication, 37% of parents reported never discussing short-term side effects such as fungal infection, sore throat, or hoarseness with their physicians; and 55% reported never discussing long-term effects including weight gain, weakening of the bones or changing bone density. This compares with physician reports of 1% and 6%, respectively. When asked who typically brings up the topic of asthma medication side effects, 62% of parents said they or their child did; 76% of physicians said they did.

For more information on the study findings, go to www.gappsurvey.org

MONTREAL — There is a disconnect in communications between physicians and parents of children with asthma, according to an analysis of data from a new global asthma survey.

Parents and physicians disagree on the amount of time dedicated to asthma education in the office; who initiates discussion about medication side effects; and the level of treatment compliance with asthma medication.

The North American pediatric findings of the Global Asthma Physician and Patient (GAPP) study also confirm what most physicians already know: Asthma medication compliance is low; patients with poor compliance experience more symptoms; and side effects lead patients to switch or drop medications.

The authors conclude that patient compliance and outcomes could be enhanced through better physician-patient communications and asthma education, and the availability of new treatment options with lower side-effect profiles, Dr. Ronald Dahl of Aarhus (Denmark) University Hospital, and his associates on the GAPP Survey Working Group reported in a poster at the Seventh International Congress on Pediatric Pulmonology.

The survey was conducted between May and August 2005 in 16 countries and included a total of 5,482 online and telephone interviews with 1,017 parents of children diagnosed with asthma, 1,006 physicians who treat children with asthma, 1,726 adults over 18 years of age with asthma, and 1,733 physicians who treat adults. It was supported by an educational grant from Altana Pharma and conducted in cooperation with the World Allergy Organization and American College of Allergy, Asthma, and Immunology. It was sufficiently powered to ensure statistical significance globally and in each country.

The analysis presented here was based on 618 interviews conducted in North America among 314 parents and 304 physicians.

Among parents interviewed, 62% reported their children's asthma as mild; 33% as moderate; and 5% as severe. In the 12 months before the interview, parents reported a number of events demonstrating poor asthma control such as making an unscheduled visit to their doctor (34%), going to the emergency department (11%), and admission to the hospital (5%).

According to parents, physicians don't discuss specific asthma management issues such as development of an individual management plan (66%); correct inhaler technique (69%); and keeping daily symptom or medication diaries (25%). Physicians' perceptions of the incidence of these exchanges were 90%, 97%, 53%, respectively.

Parents also perceive that less time is spent on asthma education than physicians perceive. Whereas 18% of parents reported that during a typical office visit, no time is spent on asthma education, about 84% of physicians report spending at least half of their office time on education.

Overall, 27% of parents answered “false” or “not sure” when asked whether mild asthma attacks could be fatal, which demonstrates a general lack of understanding about the disease, the authors reported. Global findings from the survey indicate that treatment compliance increased with the level of asthma education, a trend that also was seen in local results.

Of those patients with asthma who take or had taken asthma medication, 37% of parents reported never discussing short-term side effects such as fungal infection, sore throat, or hoarseness with their physicians; and 55% reported never discussing long-term effects including weight gain, weakening of the bones or changing bone density. This compares with physician reports of 1% and 6%, respectively. When asked who typically brings up the topic of asthma medication side effects, 62% of parents said they or their child did; 76% of physicians said they did.

For more information on the study findings, go to www.gappsurvey.org

MONTREAL — New data show that the novel inhaled corticosteroid, ciclesonide, has no detectable effect on growth, body height, or hypothalamic-pituitary-adrenal axis function when administered once daily for a year in prepubertal children with mild, persistent asthma.

The results are reassuring because all other inhaled corticosteroids have been associated with a small degree of growth suppression in pediatric patients, principle investigator Dr. David Skoner said in an interview. The study was performed using tougher clinical trial guidelines established in the late 1990s by the U.S. Food and Drug Administration, requiring larger numbers of children and longer run-in periods to gauge the effect of a steroid on growth.

“There is a lot of steroid phobia, including among doctors, that prevents people from using or adhering to steroids. This should defuse some of that phobia, improve adherence, and get better outcomes,” said Dr. Skoner, director of the division of allergy, asthma, and immunology at Allegheny General Hospital in Pittsburgh. Dr. Skoner and associates reported their data in a poster at the Seventh International Congress on Pediatric Pulmonology. Ciclesonide (Alvesco) is under development in the United States, and has been approved for the treatment of persistent asthma in adults, aged 18 years or older, in some European and South American countries.

The phase III, double-blind, multicenter study randomized 661 children (aged 5–8.5 years) to receive one puff in the morning of ciclesonide 160 mcg/day, ciclesonide 40 mcg/day, or placebo for 1 year. Of those, 52 were excluded because they did not receive treatment for 4 months or more, or had missing height data, leaving a modified intent-to-treat population of 609 patients.

There were three phases; a 6-month run-in or baseline period, a 12-month treatment period, and a 2-month follow-up period. Rescue medications, including inhaled short-acting β-2 agonists, leukotriene receptor antagonists, cromones such as cromoglycate and nedocromil, and xanthine derivatives, were permitted on an as-needed basis during the baseline and double-blind treatment periods. No corticosteroids, other than the study medication, were permitted. The overall mean growth velocity, or growth rate, was slightly lower in the ciclesonide 160 group during the baseline period, compared with that in the other two groups. All other baseline characteristics were comparable among groups.

The study's primary end point of growth velocity during the 12-month treatment period was comparable among the groups, Dr. Skoner reported. Growth velocity averaged 5.6 cm/yr in the ciclesonide 160 group; 5.73 cm/yr in the ciclesonide 40 group; and 5.75 cm/yr in the placebo group. During the follow-up period, growth velocity was 5.64 cm/yr; 6.06 cm/yr; and 5.75 cm/yr, respectively.

Cortisol measures for 308 patients showed the mean change from baseline to study end in 24-hour urinary free cortisol, corrected for creatinine levels, remained relatively unchanged in the three groups. The differences were not significant.

In a separate study in adolescents with severe asthma, investigators reported a negative impact on the hypothalamic-pituitary-adrenal axis, as assessed by a decrease in urinary free-cortisol levels, associated with budesonide 800 mcg/day but not with ciclesonide 320 mcg/day.

The randomized, double-blind, multinational study included 403 adolescents in the intent-to-treat population, 371 in the per-protocol population, and 207 in a safety analysis. Their mean age was 14 years (range 12–17 years), and there were more male than female patients in both groups.

In the safety analysis, there was a slight increase after 12 weeks of treatment in creatinine-adjusted 24-hour urinary free cortisol in the ciclesonide group. Urinary free cortisol decreased significantly in the budesonide group, Dr. J. Vermeulen of Panorama Medical Practice, Cape Town, South Africa, and associates said in a separate poster at the meeting. The study's primary end point of change in forced expiratory volume in 1 second from baseline to end of treatment was similar among the groups, increasing by 518 mL with ciclesonide and by 533 mL with budesonide.

Both studies were supported by Altana Pharma and Sanofi-Aventis, which are jointly developing and marketing ciclesonide. Dr. Skoner has served on the speakers' bureau and received grant support from Sanofi-Aventis.

MONTREAL — New data show that the novel inhaled corticosteroid, ciclesonide, has no detectable effect on growth, body height, or hypothalamic-pituitary-adrenal axis function when administered once daily for a year in prepubertal children with mild, persistent asthma.

The results are reassuring because all other inhaled corticosteroids have been associated with a small degree of growth suppression in pediatric patients, principle investigator Dr. David Skoner said in an interview. The study was performed using tougher clinical trial guidelines established in the late 1990s by the U.S. Food and Drug Administration, requiring larger numbers of children and longer run-in periods to gauge the effect of a steroid on growth.

“There is a lot of steroid phobia, including among doctors, that prevents people from using or adhering to steroids. This should defuse some of that phobia, improve adherence, and get better outcomes,” said Dr. Skoner, director of the division of allergy, asthma, and immunology at Allegheny General Hospital in Pittsburgh. Dr. Skoner and associates reported their data in a poster at the Seventh International Congress on Pediatric Pulmonology. Ciclesonide (Alvesco) is under development in the United States, and has been approved for the treatment of persistent asthma in adults, aged 18 years or older, in some European and South American countries.

The phase III, double-blind, multicenter study randomized 661 children (aged 5–8.5 years) to receive one puff in the morning of ciclesonide 160 mcg/day, ciclesonide 40 mcg/day, or placebo for 1 year. Of those, 52 were excluded because they did not receive treatment for 4 months or more, or had missing height data, leaving a modified intent-to-treat population of 609 patients.

There were three phases; a 6-month run-in or baseline period, a 12-month treatment period, and a 2-month follow-up period. Rescue medications, including inhaled short-acting β-2 agonists, leukotriene receptor antagonists, cromones such as cromoglycate and nedocromil, and xanthine derivatives, were permitted on an as-needed basis during the baseline and double-blind treatment periods. No corticosteroids, other than the study medication, were permitted. The overall mean growth velocity, or growth rate, was slightly lower in the ciclesonide 160 group during the baseline period, compared with that in the other two groups. All other baseline characteristics were comparable among groups.

The study's primary end point of growth velocity during the 12-month treatment period was comparable among the groups, Dr. Skoner reported. Growth velocity averaged 5.6 cm/yr in the ciclesonide 160 group; 5.73 cm/yr in the ciclesonide 40 group; and 5.75 cm/yr in the placebo group. During the follow-up period, growth velocity was 5.64 cm/yr; 6.06 cm/yr; and 5.75 cm/yr, respectively.

Cortisol measures for 308 patients showed the mean change from baseline to study end in 24-hour urinary free cortisol, corrected for creatinine levels, remained relatively unchanged in the three groups. The differences were not significant.

In a separate study in adolescents with severe asthma, investigators reported a negative impact on the hypothalamic-pituitary-adrenal axis, as assessed by a decrease in urinary free-cortisol levels, associated with budesonide 800 mcg/day but not with ciclesonide 320 mcg/day.

The randomized, double-blind, multinational study included 403 adolescents in the intent-to-treat population, 371 in the per-protocol population, and 207 in a safety analysis. Their mean age was 14 years (range 12–17 years), and there were more male than female patients in both groups.

In the safety analysis, there was a slight increase after 12 weeks of treatment in creatinine-adjusted 24-hour urinary free cortisol in the ciclesonide group. Urinary free cortisol decreased significantly in the budesonide group, Dr. J. Vermeulen of Panorama Medical Practice, Cape Town, South Africa, and associates said in a separate poster at the meeting. The study's primary end point of change in forced expiratory volume in 1 second from baseline to end of treatment was similar among the groups, increasing by 518 mL with ciclesonide and by 533 mL with budesonide.

Both studies were supported by Altana Pharma and Sanofi-Aventis, which are jointly developing and marketing ciclesonide. Dr. Skoner has served on the speakers' bureau and received grant support from Sanofi-Aventis.

MONTREAL — New data show that the novel inhaled corticosteroid, ciclesonide, has no detectable effect on growth, body height, or hypothalamic-pituitary-adrenal axis function when administered once daily for a year in prepubertal children with mild, persistent asthma.

The results are reassuring because all other inhaled corticosteroids have been associated with a small degree of growth suppression in pediatric patients, principle investigator Dr. David Skoner said in an interview. The study was performed using tougher clinical trial guidelines established in the late 1990s by the U.S. Food and Drug Administration, requiring larger numbers of children and longer run-in periods to gauge the effect of a steroid on growth.

“There is a lot of steroid phobia, including among doctors, that prevents people from using or adhering to steroids. This should defuse some of that phobia, improve adherence, and get better outcomes,” said Dr. Skoner, director of the division of allergy, asthma, and immunology at Allegheny General Hospital in Pittsburgh. Dr. Skoner and associates reported their data in a poster at the Seventh International Congress on Pediatric Pulmonology. Ciclesonide (Alvesco) is under development in the United States, and has been approved for the treatment of persistent asthma in adults, aged 18 years or older, in some European and South American countries.

The phase III, double-blind, multicenter study randomized 661 children (aged 5–8.5 years) to receive one puff in the morning of ciclesonide 160 mcg/day, ciclesonide 40 mcg/day, or placebo for 1 year. Of those, 52 were excluded because they did not receive treatment for 4 months or more, or had missing height data, leaving a modified intent-to-treat population of 609 patients.

There were three phases; a 6-month run-in or baseline period, a 12-month treatment period, and a 2-month follow-up period. Rescue medications, including inhaled short-acting β-2 agonists, leukotriene receptor antagonists, cromones such as cromoglycate and nedocromil, and xanthine derivatives, were permitted on an as-needed basis during the baseline and double-blind treatment periods. No corticosteroids, other than the study medication, were permitted. The overall mean growth velocity, or growth rate, was slightly lower in the ciclesonide 160 group during the baseline period, compared with that in the other two groups. All other baseline characteristics were comparable among groups.

The study's primary end point of growth velocity during the 12-month treatment period was comparable among the groups, Dr. Skoner reported. Growth velocity averaged 5.6 cm/yr in the ciclesonide 160 group; 5.73 cm/yr in the ciclesonide 40 group; and 5.75 cm/yr in the placebo group. During the follow-up period, growth velocity was 5.64 cm/yr; 6.06 cm/yr; and 5.75 cm/yr, respectively.

Cortisol measures for 308 patients showed the mean change from baseline to study end in 24-hour urinary free cortisol, corrected for creatinine levels, remained relatively unchanged in the three groups. The differences were not significant.

In a separate study in adolescents with severe asthma, investigators reported a negative impact on the hypothalamic-pituitary-adrenal axis, as assessed by a decrease in urinary free-cortisol levels, associated with budesonide 800 mcg/day but not with ciclesonide 320 mcg/day.

The randomized, double-blind, multinational study included 403 adolescents in the intent-to-treat population, 371 in the per-protocol population, and 207 in a safety analysis. Their mean age was 14 years (range 12–17 years), and there were more male than female patients in both groups.

In the safety analysis, there was a slight increase after 12 weeks of treatment in creatinine-adjusted 24-hour urinary free cortisol in the ciclesonide group. Urinary free cortisol decreased significantly in the budesonide group, Dr. J. Vermeulen of Panorama Medical Practice, Cape Town, South Africa, and associates said in a separate poster at the meeting. The study's primary end point of change in forced expiratory volume in 1 second from baseline to end of treatment was similar among the groups, increasing by 518 mL with ciclesonide and by 533 mL with budesonide.

Both studies were supported by Altana Pharma and Sanofi-Aventis, which are jointly developing and marketing ciclesonide. Dr. Skoner has served on the speakers' bureau and received grant support from Sanofi-Aventis.

NICE, FRANCE — Family physicians prescribe penicillins most often, whereas surgeons prescribe fluoroquinolones more frequently than any other specialty.

These are some of the findings from a 3-year study examining prescribing patterns of oral antibiotics by physician specialty in the United States. This is the first study to offer a national perspective on outpatient antimicrobial prescribing by physician specialty, Katie J. Suda, Pharm. D., and her associates reported at the 16th European Congress of Clinical Microbiology and Infectious Diseases.

“Over the 3 years, prescribing patterns did vary significantly by physician specialty,” she said.

Investigators evaluated outpatient antibiotic prescriptions dispensed in 2001–2003 from nine managed health care plans. Medications were stratified into classes and formulations as defined by the American Hospital Formulary Service. Diagnostic codes were defined according to Medicode (now Ingenix).

A total of 7,613 physicians wrote 48,182 antibiotic prescriptions for 26,875 patients. The average patient age was 34 years.

The majority of patients were diagnosed with upper respiratory tract infection followed by sinusitis and genitourinary infections.

Physician specialties included family practice (42%), internal medicine (14%), pediatrics (21%), emergency medicine (5%), specialists (5%), dermatologists (4%), obstetricians/gynecologists (3%), surgeons (3%), and others such as pathologists and psychiatrists (3%).

Overall, penicillins were dispensed most frequently, followed by macrolides, cephalosporins, and fluoroquinolones, said Dr. Suda, of the University of Tennessee Health Science Center in Memphis.

Dermatologists most often prescribed tetracyclines (75%); emergency medicine physicians, macrolides (42%); ob.gyns, nitrofurans (27%); pediatricians, penicillins (38%); and surgeons, fluoroquinolones (25%). Family physicians prescribed penicillins most often, while internists prescribed fluoroquinolones.

All physician groups prescribed β-lactamase inhibitors more frequently than any other agent for the treatment of skin and skin structure infections.

Internists prescribed broader-spectrum agents for the treatment of urinary tract infections, whereas ob.gyns. prescribed narrower-spectrum agents, even though not all of their patients may be pregnant or lactating, she said.

Fluoroquinolones were used most often for UTIs by family physicians, internists, and emergency physicians, and nitrofurans by ob.gyns. and surgeons.

Beta-lactamase inhibitors were the treatment of choice for upper respiratory tract infections for family practitioners and specialists.

But internists and emergency physicians were more likely to prescribe macrolides, which may be because these physicians see more patients with complicated conditions, she said.

Pediatricians used penicillins most often, followed by macrolides and beta-lactamase inhibitors.

Overall, lower respiratory tract infections were treated most often with macrolides, followed by fluoroquinolones.

Audience members questioned whether the findings were representative of family care in the United States, particularly in light of the high fluoroquinolone use that was reported.

Dr. Suda said she believed the findings were representative of a managed care population under the age of 65 years, but added that she was unable to validate the findings against data from other plans because most organizations won't release the information.

The most commonly prescribed fluoroquinolones were levofloxacin (more than 50%), followed by ciprofloxacin, moxifloxacin, and gatifloxacin, she said.

NICE, FRANCE — Family physicians prescribe penicillins most often, whereas surgeons prescribe fluoroquinolones more frequently than any other specialty.

These are some of the findings from a 3-year study examining prescribing patterns of oral antibiotics by physician specialty in the United States. This is the first study to offer a national perspective on outpatient antimicrobial prescribing by physician specialty, Katie J. Suda, Pharm. D., and her associates reported at the 16th European Congress of Clinical Microbiology and Infectious Diseases.

“Over the 3 years, prescribing patterns did vary significantly by physician specialty,” she said.

Investigators evaluated outpatient antibiotic prescriptions dispensed in 2001–2003 from nine managed health care plans. Medications were stratified into classes and formulations as defined by the American Hospital Formulary Service. Diagnostic codes were defined according to Medicode (now Ingenix).

A total of 7,613 physicians wrote 48,182 antibiotic prescriptions for 26,875 patients. The average patient age was 34 years.

The majority of patients were diagnosed with upper respiratory tract infection followed by sinusitis and genitourinary infections.

Physician specialties included family practice (42%), internal medicine (14%), pediatrics (21%), emergency medicine (5%), specialists (5%), dermatologists (4%), obstetricians/gynecologists (3%), surgeons (3%), and others such as pathologists and psychiatrists (3%).

Overall, penicillins were dispensed most frequently, followed by macrolides, cephalosporins, and fluoroquinolones, said Dr. Suda, of the University of Tennessee Health Science Center in Memphis.

Dermatologists most often prescribed tetracyclines (75%); emergency medicine physicians, macrolides (42%); ob.gyns, nitrofurans (27%); pediatricians, penicillins (38%); and surgeons, fluoroquinolones (25%). Family physicians prescribed penicillins most often, while internists prescribed fluoroquinolones.

All physician groups prescribed β-lactamase inhibitors more frequently than any other agent for the treatment of skin and skin structure infections.

Internists prescribed broader-spectrum agents for the treatment of urinary tract infections, whereas ob.gyns. prescribed narrower-spectrum agents, even though not all of their patients may be pregnant or lactating, she said.

Fluoroquinolones were used most often for UTIs by family physicians, internists, and emergency physicians, and nitrofurans by ob.gyns. and surgeons.

Beta-lactamase inhibitors were the treatment of choice for upper respiratory tract infections for family practitioners and specialists.

But internists and emergency physicians were more likely to prescribe macrolides, which may be because these physicians see more patients with complicated conditions, she said.

Pediatricians used penicillins most often, followed by macrolides and beta-lactamase inhibitors.

Overall, lower respiratory tract infections were treated most often with macrolides, followed by fluoroquinolones.

Audience members questioned whether the findings were representative of family care in the United States, particularly in light of the high fluoroquinolone use that was reported.

Dr. Suda said she believed the findings were representative of a managed care population under the age of 65 years, but added that she was unable to validate the findings against data from other plans because most organizations won't release the information.

The most commonly prescribed fluoroquinolones were levofloxacin (more than 50%), followed by ciprofloxacin, moxifloxacin, and gatifloxacin, she said.

NICE, FRANCE — Family physicians prescribe penicillins most often, whereas surgeons prescribe fluoroquinolones more frequently than any other specialty.

These are some of the findings from a 3-year study examining prescribing patterns of oral antibiotics by physician specialty in the United States. This is the first study to offer a national perspective on outpatient antimicrobial prescribing by physician specialty, Katie J. Suda, Pharm. D., and her associates reported at the 16th European Congress of Clinical Microbiology and Infectious Diseases.

“Over the 3 years, prescribing patterns did vary significantly by physician specialty,” she said.

Investigators evaluated outpatient antibiotic prescriptions dispensed in 2001–2003 from nine managed health care plans. Medications were stratified into classes and formulations as defined by the American Hospital Formulary Service. Diagnostic codes were defined according to Medicode (now Ingenix).

A total of 7,613 physicians wrote 48,182 antibiotic prescriptions for 26,875 patients. The average patient age was 34 years.

The majority of patients were diagnosed with upper respiratory tract infection followed by sinusitis and genitourinary infections.

Physician specialties included family practice (42%), internal medicine (14%), pediatrics (21%), emergency medicine (5%), specialists (5%), dermatologists (4%), obstetricians/gynecologists (3%), surgeons (3%), and others such as pathologists and psychiatrists (3%).

Overall, penicillins were dispensed most frequently, followed by macrolides, cephalosporins, and fluoroquinolones, said Dr. Suda, of the University of Tennessee Health Science Center in Memphis.

Dermatologists most often prescribed tetracyclines (75%); emergency medicine physicians, macrolides (42%); ob.gyns, nitrofurans (27%); pediatricians, penicillins (38%); and surgeons, fluoroquinolones (25%). Family physicians prescribed penicillins most often, while internists prescribed fluoroquinolones.

All physician groups prescribed β-lactamase inhibitors more frequently than any other agent for the treatment of skin and skin structure infections.

Internists prescribed broader-spectrum agents for the treatment of urinary tract infections, whereas ob.gyns. prescribed narrower-spectrum agents, even though not all of their patients may be pregnant or lactating, she said.

Fluoroquinolones were used most often for UTIs by family physicians, internists, and emergency physicians, and nitrofurans by ob.gyns. and surgeons.

Beta-lactamase inhibitors were the treatment of choice for upper respiratory tract infections for family practitioners and specialists.

But internists and emergency physicians were more likely to prescribe macrolides, which may be because these physicians see more patients with complicated conditions, she said.

Pediatricians used penicillins most often, followed by macrolides and beta-lactamase inhibitors.

Overall, lower respiratory tract infections were treated most often with macrolides, followed by fluoroquinolones.

Audience members questioned whether the findings were representative of family care in the United States, particularly in light of the high fluoroquinolone use that was reported.

Dr. Suda said she believed the findings were representative of a managed care population under the age of 65 years, but added that she was unable to validate the findings against data from other plans because most organizations won't release the information.

The most commonly prescribed fluoroquinolones were levofloxacin (more than 50%), followed by ciprofloxacin, moxifloxacin, and gatifloxacin, she said.

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims said at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained the shot was free, available at a nurse visit, and could be scheduled if desired. The nurses also asked why the patient had not been immunized, then gave information tailored to the reason mentioned by the participant. Most commonly, patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%), but immunization rates improved significantly in both populations. Most patients received their pneumococcal vaccine within 3 months of the outreach.

The cost of the phone calls was $41,520, or $147 per additional patient vaccinated, compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which averages about $5,000.

Kaiser Permanente in Atlanta had previously tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters and clinic posters. Those efforts significantly improved immunization rates, to 60% in seniors and about 40%–45% in younger, chronically ill patients. But the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%.

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims said at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained the shot was free, available at a nurse visit, and could be scheduled if desired. The nurses also asked why the patient had not been immunized, then gave information tailored to the reason mentioned by the participant. Most commonly, patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%), but immunization rates improved significantly in both populations. Most patients received their pneumococcal vaccine within 3 months of the outreach.

The cost of the phone calls was $41,520, or $147 per additional patient vaccinated, compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which averages about $5,000.

Kaiser Permanente in Atlanta had previously tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters and clinic posters. Those efforts significantly improved immunization rates, to 60% in seniors and about 40%–45% in younger, chronically ill patients. But the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%.

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims said at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained the shot was free, available at a nurse visit, and could be scheduled if desired. The nurses also asked why the patient had not been immunized, then gave information tailored to the reason mentioned by the participant. Most commonly, patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%), but immunization rates improved significantly in both populations. Most patients received their pneumococcal vaccine within 3 months of the outreach.

The cost of the phone calls was $41,520, or $147 per additional patient vaccinated, compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which averages about $5,000.

Kaiser Permanente in Atlanta had previously tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters and clinic posters. Those efforts significantly improved immunization rates, to 60% in seniors and about 40%–45% in younger, chronically ill patients. But the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%.

PITTSBURGH – Interventions to reduce or neutralize proinflammatory cytokines may be novel treatments in patients with sleep disorders and obesity, Dr. Alexandros Vgontas said at the International Congress of Neuroendocrinology.

Three inflammation-associated cytokines–tumor necrosis factor-α (TNF-α, interleukin-1 (IL-1), and IL-6–are elevated in obese and sleep-deprived patients, and may mediate excessive daytime sleepiness and fatigue. All three cytokines are part of the acute phase response and activate the hypothalamic-pituitary-adrenal axis.

“Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance, obesity, and cardiovascular problems,” said Dr. Vgontas, director of the Center for Sleep Disorders Medicine and professor of psychiatry at Pennsylvania State College of Medicine in Hershey.

Over the last decade, research has focused on the role of proinflammatory cytokines in sleep loss and sleep disorders such as sleep apnea, narcolepsy, and insomnia. Studies have demonstrated that IL-6 and TNF-α plasma levels are elevated in patients with sleep apnea and narcolepsy, he said.

Dr. Vgontas and his colleagues also reported a positive correlation between IL-6 and TNF-α levels and body mass index. In a study in 73 obese patients and 45 healthy controls, both without sleep-disordered breathing, obese patients were significantly more likely to have excessive daytime sleepiness.

The finding was replicated by investigators at Pennsylvania State in a large, random community sample in which the strongest risk factors for excessive daytime sleepiness were depression, body mass index, age, sleep duration, diabetes, and finally sleep apnea (J. Clin. Endocrinol. Metab. 2005;90:4510–5).

Dr. Vgontas also studied women with polycystic ovary syndrome, a condition in which the primary pathogenetic mechanism is insulin resistance. In that study, he found that daytime sleepiness is present in 80% of women who have PCOS, and that there is a 30-fold increase in sleep apnea in this population, compared with healthy controls.

Based on these findings, he postulated that sleep apnea is primarily a manifestation of metabolic syndrome rather than a local abnormality of the respiratory track. TNF-α IL-1, and IL-6 are produced by adipose tissue, particularly visceral fat, where 30% of IL-6 is produced. CT scans have shown that sleep apnea patients have significantly more visceral fat in the abdominal area than do obese patients without sleep apnea, Dr. Vgontas said.

Several outside studies also support this systemic view of cytokines in sleep disorders and related health problems. One study showed that sleep apnea patients are more insulin resistant, older, and more obese, but also that insulin resistance is present even in nonobese apnea patients (Am. J. Respir. Crit. Care Med. 2002;165:670–6). Another study indicates that insulin resistance is present even in mild forms of sleep apnea (Am. J. Respir. Crit. Care Med. 2002;165:677–82).

Interventions in this area remain limited. The use of IL-1 or TNF-α receptor antagonists or IL-1b antibodies has been shown to reduce sleep in an animal model. A small pilot study in humans showed that the use of etanercept, a cytokine antagonist, decreased sleepiness in eight obese men with symptomatic apnea, Dr. Vgontas reported.

'Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance.' DR. VGONTAS

PITTSBURGH – Interventions to reduce or neutralize proinflammatory cytokines may be novel treatments in patients with sleep disorders and obesity, Dr. Alexandros Vgontas said at the International Congress of Neuroendocrinology.

Three inflammation-associated cytokines–tumor necrosis factor-α (TNF-α, interleukin-1 (IL-1), and IL-6–are elevated in obese and sleep-deprived patients, and may mediate excessive daytime sleepiness and fatigue. All three cytokines are part of the acute phase response and activate the hypothalamic-pituitary-adrenal axis.

“Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance, obesity, and cardiovascular problems,” said Dr. Vgontas, director of the Center for Sleep Disorders Medicine and professor of psychiatry at Pennsylvania State College of Medicine in Hershey.

Over the last decade, research has focused on the role of proinflammatory cytokines in sleep loss and sleep disorders such as sleep apnea, narcolepsy, and insomnia. Studies have demonstrated that IL-6 and TNF-α plasma levels are elevated in patients with sleep apnea and narcolepsy, he said.

Dr. Vgontas and his colleagues also reported a positive correlation between IL-6 and TNF-α levels and body mass index. In a study in 73 obese patients and 45 healthy controls, both without sleep-disordered breathing, obese patients were significantly more likely to have excessive daytime sleepiness.

The finding was replicated by investigators at Pennsylvania State in a large, random community sample in which the strongest risk factors for excessive daytime sleepiness were depression, body mass index, age, sleep duration, diabetes, and finally sleep apnea (J. Clin. Endocrinol. Metab. 2005;90:4510–5).

Dr. Vgontas also studied women with polycystic ovary syndrome, a condition in which the primary pathogenetic mechanism is insulin resistance. In that study, he found that daytime sleepiness is present in 80% of women who have PCOS, and that there is a 30-fold increase in sleep apnea in this population, compared with healthy controls.

Based on these findings, he postulated that sleep apnea is primarily a manifestation of metabolic syndrome rather than a local abnormality of the respiratory track. TNF-α IL-1, and IL-6 are produced by adipose tissue, particularly visceral fat, where 30% of IL-6 is produced. CT scans have shown that sleep apnea patients have significantly more visceral fat in the abdominal area than do obese patients without sleep apnea, Dr. Vgontas said.

Several outside studies also support this systemic view of cytokines in sleep disorders and related health problems. One study showed that sleep apnea patients are more insulin resistant, older, and more obese, but also that insulin resistance is present even in nonobese apnea patients (Am. J. Respir. Crit. Care Med. 2002;165:670–6). Another study indicates that insulin resistance is present even in mild forms of sleep apnea (Am. J. Respir. Crit. Care Med. 2002;165:677–82).

Interventions in this area remain limited. The use of IL-1 or TNF-α receptor antagonists or IL-1b antibodies has been shown to reduce sleep in an animal model. A small pilot study in humans showed that the use of etanercept, a cytokine antagonist, decreased sleepiness in eight obese men with symptomatic apnea, Dr. Vgontas reported.

'Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance.' DR. VGONTAS

PITTSBURGH – Interventions to reduce or neutralize proinflammatory cytokines may be novel treatments in patients with sleep disorders and obesity, Dr. Alexandros Vgontas said at the International Congress of Neuroendocrinology.

Three inflammation-associated cytokines–tumor necrosis factor-α (TNF-α, interleukin-1 (IL-1), and IL-6–are elevated in obese and sleep-deprived patients, and may mediate excessive daytime sleepiness and fatigue. All three cytokines are part of the acute phase response and activate the hypothalamic-pituitary-adrenal axis.

“Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance, obesity, and cardiovascular problems,” said Dr. Vgontas, director of the Center for Sleep Disorders Medicine and professor of psychiatry at Pennsylvania State College of Medicine in Hershey.

Over the last decade, research has focused on the role of proinflammatory cytokines in sleep loss and sleep disorders such as sleep apnea, narcolepsy, and insomnia. Studies have demonstrated that IL-6 and TNF-α plasma levels are elevated in patients with sleep apnea and narcolepsy, he said.

Dr. Vgontas and his colleagues also reported a positive correlation between IL-6 and TNF-α levels and body mass index. In a study in 73 obese patients and 45 healthy controls, both without sleep-disordered breathing, obese patients were significantly more likely to have excessive daytime sleepiness.

The finding was replicated by investigators at Pennsylvania State in a large, random community sample in which the strongest risk factors for excessive daytime sleepiness were depression, body mass index, age, sleep duration, diabetes, and finally sleep apnea (J. Clin. Endocrinol. Metab. 2005;90:4510–5).

Dr. Vgontas also studied women with polycystic ovary syndrome, a condition in which the primary pathogenetic mechanism is insulin resistance. In that study, he found that daytime sleepiness is present in 80% of women who have PCOS, and that there is a 30-fold increase in sleep apnea in this population, compared with healthy controls.

Based on these findings, he postulated that sleep apnea is primarily a manifestation of metabolic syndrome rather than a local abnormality of the respiratory track. TNF-α IL-1, and IL-6 are produced by adipose tissue, particularly visceral fat, where 30% of IL-6 is produced. CT scans have shown that sleep apnea patients have significantly more visceral fat in the abdominal area than do obese patients without sleep apnea, Dr. Vgontas said.

Several outside studies also support this systemic view of cytokines in sleep disorders and related health problems. One study showed that sleep apnea patients are more insulin resistant, older, and more obese, but also that insulin resistance is present even in nonobese apnea patients (Am. J. Respir. Crit. Care Med. 2002;165:670–6). Another study indicates that insulin resistance is present even in mild forms of sleep apnea (Am. J. Respir. Crit. Care Med. 2002;165:677–82).

Interventions in this area remain limited. The use of IL-1 or TNF-α receptor antagonists or IL-1b antibodies has been shown to reduce sleep in an animal model. A small pilot study in humans showed that the use of etanercept, a cytokine antagonist, decreased sleepiness in eight obese men with symptomatic apnea, Dr. Vgontas reported.

'Proinflammatory cytokines may represent a pathophysiologic link to insulin resistance.' DR. VGONTAS

PITTSBURGH – Adolescence is physically the healthiest period of the life span, but early adolescence appears to be a time of developmental vulnerability in relation to sleep, arousal, and emotional regulation, Dr. Ronald E. Dahl said at the International Congress of Neuroendocrinology.

This key phase of development has broad relevance to adolescent behavioral and emotional health, and should be viewed as a time of opportunity for early intervention.

Dr. Dahl and his colleagues at Western Psychiatric Institute and Clinic in Pittsburgh carried out a series of studies in children and adolescents, aged 8–16, with affective disorders that included several measures of sleep and hypothalamic-pituitary-adrenal (HPA) axis regulation.

The subjects included 128 children studied during an episode of depression, 102 children with anxiety disorders, and 102 age-matched controls who were medically and psychiatrically healthy and had negative family histories for depression.

Despite extensive subjective sleep complaints in depressed children and adolescents, younger prepubertal adolescents showed little or no objective evidence of sleep and cortisol dysregulation.

But midpubertal and older adolescents with major depressive disorder revealed evidence of EEG sleep and cortisol changes associated with adult depression, including increased sleep latency, decreased REM-latency, increased REM-density, and cortisol and growth hormone changes near sleep onset.

Increased cortisol near sleep onset and REM density were predictive of future episodes of depression, said Dr. Dahl, also the Staunton Professor of Psychiatry and Pediatrics at the University of Pittsburgh.

In contrast, children with anxiety disorders showed evidence of earlier EEG sleep and cortisol changes. The anxiety group took significantly longer to fall asleep, had less total sleep time, less slow-wave sleep, and higher levels of cortisol at bedtime, compared with the healthy controls and with children with depression.

Some changes in sleep regulation are biologic and linked to puberty; others are linked to social habits and environmental influences. Puberty is marked by increased daytime sleepiness, while changes in biologic timing systems related to the circadian system push adolescents toward more owl-like tendencies to stay up late and sleep in late.

At the same time, an increasing number of adolescents have access to stimulating activities in their bedrooms, such as MP3 players, electronic or video games, and cell phones. In addition, more are drinking caffeinated beverages. “Spiraling interactions between these domains can lead to vulnerability and spiral into serious clinical problems,” Dr. Dahl said at the meeting, sponsored by the University of Pittsburgh and the American Neuroendocrine Society.

According to a National Science Foundation national sleep poll, 45% of adolescents and 62% of 9th-12th grade adolescents get an insufficient amount of sleep on school nights, averaging about 6.9 hours in the 12th grade. More than 10% of U.S. high school seniors must get up before 5:30 a.m. to catch buses.

Sleepiness and tiredness are well-known consequences of this school-sleep squeeze, he said. But sleep-deprived adolescents also suffer irritability, emotional lability, difficulties with affect regulation and cognitive-emotional integration, and deleterious direct effects on learning and memory consolidation.

A recently published study in incarcerated male juvenile and young offenders found that aggression was related to both quantity and quality of sleep (J. Adolesc. Health 2006;38:649–55).

Preliminary data from a second study indicate that inadequate sleep in substance-abusing adolescents may contribute to their experiencing aggressive thoughts and actions (Sleep 2006;29:512–20). Dr. Dahl called these results provocative not only because of the correlation between sleep and aggression but also because the study demonstrated that a 6-week integrative behavioral sleep intervention could decrease the frequency of reported aggressive thoughts and actions.

Such research raises compelling questions about specific mechanisms of sleep and affective changes, with the long-term goal of informing early intervention in high-risk populations at key points in development, Dr. Dahl said.

Preliminary data from a study of inadequate sleep in substance-abusing teens are provocative. DR. DAHL

PITTSBURGH – Adolescence is physically the healthiest period of the life span, but early adolescence appears to be a time of developmental vulnerability in relation to sleep, arousal, and emotional regulation, Dr. Ronald E. Dahl said at the International Congress of Neuroendocrinology.

This key phase of development has broad relevance to adolescent behavioral and emotional health, and should be viewed as a time of opportunity for early intervention.

Dr. Dahl and his colleagues at Western Psychiatric Institute and Clinic in Pittsburgh carried out a series of studies in children and adolescents, aged 8–16, with affective disorders that included several measures of sleep and hypothalamic-pituitary-adrenal (HPA) axis regulation.

The subjects included 128 children studied during an episode of depression, 102 children with anxiety disorders, and 102 age-matched controls who were medically and psychiatrically healthy and had negative family histories for depression.

Despite extensive subjective sleep complaints in depressed children and adolescents, younger prepubertal adolescents showed little or no objective evidence of sleep and cortisol dysregulation.

But midpubertal and older adolescents with major depressive disorder revealed evidence of EEG sleep and cortisol changes associated with adult depression, including increased sleep latency, decreased REM-latency, increased REM-density, and cortisol and growth hormone changes near sleep onset.

Increased cortisol near sleep onset and REM density were predictive of future episodes of depression, said Dr. Dahl, also the Staunton Professor of Psychiatry and Pediatrics at the University of Pittsburgh.

In contrast, children with anxiety disorders showed evidence of earlier EEG sleep and cortisol changes. The anxiety group took significantly longer to fall asleep, had less total sleep time, less slow-wave sleep, and higher levels of cortisol at bedtime, compared with the healthy controls and with children with depression.

Some changes in sleep regulation are biologic and linked to puberty; others are linked to social habits and environmental influences. Puberty is marked by increased daytime sleepiness, while changes in biologic timing systems related to the circadian system push adolescents toward more owl-like tendencies to stay up late and sleep in late.

At the same time, an increasing number of adolescents have access to stimulating activities in their bedrooms, such as MP3 players, electronic or video games, and cell phones. In addition, more are drinking caffeinated beverages. “Spiraling interactions between these domains can lead to vulnerability and spiral into serious clinical problems,” Dr. Dahl said at the meeting, sponsored by the University of Pittsburgh and the American Neuroendocrine Society.

According to a National Science Foundation national sleep poll, 45% of adolescents and 62% of 9th-12th grade adolescents get an insufficient amount of sleep on school nights, averaging about 6.9 hours in the 12th grade. More than 10% of U.S. high school seniors must get up before 5:30 a.m. to catch buses.

Sleepiness and tiredness are well-known consequences of this school-sleep squeeze, he said. But sleep-deprived adolescents also suffer irritability, emotional lability, difficulties with affect regulation and cognitive-emotional integration, and deleterious direct effects on learning and memory consolidation.

A recently published study in incarcerated male juvenile and young offenders found that aggression was related to both quantity and quality of sleep (J. Adolesc. Health 2006;38:649–55).

Preliminary data from a second study indicate that inadequate sleep in substance-abusing adolescents may contribute to their experiencing aggressive thoughts and actions (Sleep 2006;29:512–20). Dr. Dahl called these results provocative not only because of the correlation between sleep and aggression but also because the study demonstrated that a 6-week integrative behavioral sleep intervention could decrease the frequency of reported aggressive thoughts and actions.

Such research raises compelling questions about specific mechanisms of sleep and affective changes, with the long-term goal of informing early intervention in high-risk populations at key points in development, Dr. Dahl said.

Preliminary data from a study of inadequate sleep in substance-abusing teens are provocative. DR. DAHL

PITTSBURGH – Adolescence is physically the healthiest period of the life span, but early adolescence appears to be a time of developmental vulnerability in relation to sleep, arousal, and emotional regulation, Dr. Ronald E. Dahl said at the International Congress of Neuroendocrinology.

This key phase of development has broad relevance to adolescent behavioral and emotional health, and should be viewed as a time of opportunity for early intervention.

Dr. Dahl and his colleagues at Western Psychiatric Institute and Clinic in Pittsburgh carried out a series of studies in children and adolescents, aged 8–16, with affective disorders that included several measures of sleep and hypothalamic-pituitary-adrenal (HPA) axis regulation.

The subjects included 128 children studied during an episode of depression, 102 children with anxiety disorders, and 102 age-matched controls who were medically and psychiatrically healthy and had negative family histories for depression.

Despite extensive subjective sleep complaints in depressed children and adolescents, younger prepubertal adolescents showed little or no objective evidence of sleep and cortisol dysregulation.

But midpubertal and older adolescents with major depressive disorder revealed evidence of EEG sleep and cortisol changes associated with adult depression, including increased sleep latency, decreased REM-latency, increased REM-density, and cortisol and growth hormone changes near sleep onset.

Increased cortisol near sleep onset and REM density were predictive of future episodes of depression, said Dr. Dahl, also the Staunton Professor of Psychiatry and Pediatrics at the University of Pittsburgh.

In contrast, children with anxiety disorders showed evidence of earlier EEG sleep and cortisol changes. The anxiety group took significantly longer to fall asleep, had less total sleep time, less slow-wave sleep, and higher levels of cortisol at bedtime, compared with the healthy controls and with children with depression.

Some changes in sleep regulation are biologic and linked to puberty; others are linked to social habits and environmental influences. Puberty is marked by increased daytime sleepiness, while changes in biologic timing systems related to the circadian system push adolescents toward more owl-like tendencies to stay up late and sleep in late.

At the same time, an increasing number of adolescents have access to stimulating activities in their bedrooms, such as MP3 players, electronic or video games, and cell phones. In addition, more are drinking caffeinated beverages. “Spiraling interactions between these domains can lead to vulnerability and spiral into serious clinical problems,” Dr. Dahl said at the meeting, sponsored by the University of Pittsburgh and the American Neuroendocrine Society.

According to a National Science Foundation national sleep poll, 45% of adolescents and 62% of 9th-12th grade adolescents get an insufficient amount of sleep on school nights, averaging about 6.9 hours in the 12th grade. More than 10% of U.S. high school seniors must get up before 5:30 a.m. to catch buses.

Sleepiness and tiredness are well-known consequences of this school-sleep squeeze, he said. But sleep-deprived adolescents also suffer irritability, emotional lability, difficulties with affect regulation and cognitive-emotional integration, and deleterious direct effects on learning and memory consolidation.

A recently published study in incarcerated male juvenile and young offenders found that aggression was related to both quantity and quality of sleep (J. Adolesc. Health 2006;38:649–55).

Preliminary data from a second study indicate that inadequate sleep in substance-abusing adolescents may contribute to their experiencing aggressive thoughts and actions (Sleep 2006;29:512–20). Dr. Dahl called these results provocative not only because of the correlation between sleep and aggression but also because the study demonstrated that a 6-week integrative behavioral sleep intervention could decrease the frequency of reported aggressive thoughts and actions.

Such research raises compelling questions about specific mechanisms of sleep and affective changes, with the long-term goal of informing early intervention in high-risk populations at key points in development, Dr. Dahl said.

Preliminary data from a study of inadequate sleep in substance-abusing teens are provocative. DR. DAHL

MONTREAL — The first long-term follow-up of infants with bronchopulmonary dysplasia suggests that the consequences of preterm birth lessen over time, but are enduring.

“The consequences of preterm birth clearly seem to lessen over time going from the newborn period into early adult life; but being small for gestational age and preterm, the effects are much more long-lasting, both in terms of airflow obstruction and cardiovascular reprogramming,” Dr. Andrew Bush said at the International Congress on Pediatric Pulmonology.

The analysis included 60 adults, aged 20–22 years, from an original cohort of 300 babies with chronic lung disease of prematurity, and 50 new, age-matched term controls. The preterm group included 23 adults who were defined as small for gestational age (less than 1,500 g) and 37 defined as appropriate for gestational age (1,500–2,000 g). Evaluations included spirometry, exhaled nitric oxide testing, skin-prick tests, and exercise tests.

Forced expiratory volume in 1 second (FEV₁) z scores were not significantly different among the three groups. But when those scores were plotted by birth weight, birth weight was found to be a significant determinant of FEV₁ outcomes for preterm small-for-gestational-age (SGA) babies even after 20 years of environmental influences and self-abuse, said Dr. Bush, professor, National Heart and Lung Institute, Royal Brompton Hospital, London.

Birth weight also was a determinant of FEV_25–75 scores in this group. No association between birth weight and lung function was found in preterm appropriate-for-size survivors or controls, he said.

Using respiratory mass spectrometry, the investigators, led by Indra Narang, also of Royal Brompton Hospital, measured cardiac output and carbon monoxide transfer (DLCO). During exercise in healthy subjects, there can be a fivefold rise in cardiac output as a result of increases in both heart rate and stroke volume. DLCO can increase by up to 50% because of recruitment and distention of the pulmonary capillaries, particularly in the upper airways.

Both cardiac output and DLCO were reduced at rest, but normalized on exercise in preterm SGA survivors. Here, too, these findings were not present in the other groups.

Dr. Bush hypothesized that an adaptive mechanism may be at work.

“Is it possible that being SGA in utero you're programmed to protect your brain and kidneys at times of starvation, at times of low oxygen supply, and that this effect is persisting into adult life; so that at rest you have persistent low blood flow as an adaptive mechanism that's been programmed into you before birth?” he suggested. “I emphasize this is tentative and hypothesis generating.”

Dr. Bush acknowledged that the follow-up numbers are small, but called the findings intriguing. Questions for the future include how to monitor this aging preterm population; will their lung function deteriorate faster as they age, putting them at higher risk for chronic obstructive pulmonary disease; and how to address new bronchopulmonary consequences that will arise as neonatologists become more skilled at salvaging even more immature babies.

Cardiac output was reduced at rest, but normalized on exercise in preterm SGA survivors. DR. BUSH

MONTREAL — The first long-term follow-up of infants with bronchopulmonary dysplasia suggests that the consequences of preterm birth lessen over time, but are enduring.

“The consequences of preterm birth clearly seem to lessen over time going from the newborn period into early adult life; but being small for gestational age and preterm, the effects are much more long-lasting, both in terms of airflow obstruction and cardiovascular reprogramming,” Dr. Andrew Bush said at the International Congress on Pediatric Pulmonology.

The analysis included 60 adults, aged 20–22 years, from an original cohort of 300 babies with chronic lung disease of prematurity, and 50 new, age-matched term controls. The preterm group included 23 adults who were defined as small for gestational age (less than 1,500 g) and 37 defined as appropriate for gestational age (1,500–2,000 g). Evaluations included spirometry, exhaled nitric oxide testing, skin-prick tests, and exercise tests.

Forced expiratory volume in 1 second (FEV₁) z scores were not significantly different among the three groups. But when those scores were plotted by birth weight, birth weight was found to be a significant determinant of FEV₁ outcomes for preterm small-for-gestational-age (SGA) babies even after 20 years of environmental influences and self-abuse, said Dr. Bush, professor, National Heart and Lung Institute, Royal Brompton Hospital, London.

Birth weight also was a determinant of FEV_25–75 scores in this group. No association between birth weight and lung function was found in preterm appropriate-for-size survivors or controls, he said.

Using respiratory mass spectrometry, the investigators, led by Indra Narang, also of Royal Brompton Hospital, measured cardiac output and carbon monoxide transfer (DLCO). During exercise in healthy subjects, there can be a fivefold rise in cardiac output as a result of increases in both heart rate and stroke volume. DLCO can increase by up to 50% because of recruitment and distention of the pulmonary capillaries, particularly in the upper airways.

Both cardiac output and DLCO were reduced at rest, but normalized on exercise in preterm SGA survivors. Here, too, these findings were not present in the other groups.

Dr. Bush hypothesized that an adaptive mechanism may be at work.

“Is it possible that being SGA in utero you're programmed to protect your brain and kidneys at times of starvation, at times of low oxygen supply, and that this effect is persisting into adult life; so that at rest you have persistent low blood flow as an adaptive mechanism that's been programmed into you before birth?” he suggested. “I emphasize this is tentative and hypothesis generating.”

Dr. Bush acknowledged that the follow-up numbers are small, but called the findings intriguing. Questions for the future include how to monitor this aging preterm population; will their lung function deteriorate faster as they age, putting them at higher risk for chronic obstructive pulmonary disease; and how to address new bronchopulmonary consequences that will arise as neonatologists become more skilled at salvaging even more immature babies.

Cardiac output was reduced at rest, but normalized on exercise in preterm SGA survivors. DR. BUSH

MONTREAL — The first long-term follow-up of infants with bronchopulmonary dysplasia suggests that the consequences of preterm birth lessen over time, but are enduring.

“The consequences of preterm birth clearly seem to lessen over time going from the newborn period into early adult life; but being small for gestational age and preterm, the effects are much more long-lasting, both in terms of airflow obstruction and cardiovascular reprogramming,” Dr. Andrew Bush said at the International Congress on Pediatric Pulmonology.

The analysis included 60 adults, aged 20–22 years, from an original cohort of 300 babies with chronic lung disease of prematurity, and 50 new, age-matched term controls. The preterm group included 23 adults who were defined as small for gestational age (less than 1,500 g) and 37 defined as appropriate for gestational age (1,500–2,000 g). Evaluations included spirometry, exhaled nitric oxide testing, skin-prick tests, and exercise tests.

Forced expiratory volume in 1 second (FEV₁) z scores were not significantly different among the three groups. But when those scores were plotted by birth weight, birth weight was found to be a significant determinant of FEV₁ outcomes for preterm small-for-gestational-age (SGA) babies even after 20 years of environmental influences and self-abuse, said Dr. Bush, professor, National Heart and Lung Institute, Royal Brompton Hospital, London.

Birth weight also was a determinant of FEV_25–75 scores in this group. No association between birth weight and lung function was found in preterm appropriate-for-size survivors or controls, he said.

Using respiratory mass spectrometry, the investigators, led by Indra Narang, also of Royal Brompton Hospital, measured cardiac output and carbon monoxide transfer (DLCO). During exercise in healthy subjects, there can be a fivefold rise in cardiac output as a result of increases in both heart rate and stroke volume. DLCO can increase by up to 50% because of recruitment and distention of the pulmonary capillaries, particularly in the upper airways.

Both cardiac output and DLCO were reduced at rest, but normalized on exercise in preterm SGA survivors. Here, too, these findings were not present in the other groups.

Dr. Bush hypothesized that an adaptive mechanism may be at work.

“Is it possible that being SGA in utero you're programmed to protect your brain and kidneys at times of starvation, at times of low oxygen supply, and that this effect is persisting into adult life; so that at rest you have persistent low blood flow as an adaptive mechanism that's been programmed into you before birth?” he suggested. “I emphasize this is tentative and hypothesis generating.”

Dr. Bush acknowledged that the follow-up numbers are small, but called the findings intriguing. Questions for the future include how to monitor this aging preterm population; will their lung function deteriorate faster as they age, putting them at higher risk for chronic obstructive pulmonary disease; and how to address new bronchopulmonary consequences that will arise as neonatologists become more skilled at salvaging even more immature babies.

Cardiac output was reduced at rest, but normalized on exercise in preterm SGA survivors. DR. BUSH

PITTSBURGH — Pregnant women with anxiety or depression have higher levels of α-amylase, a measure of adrenergic system activity, and lower morning cortisol levels, preliminary results from a longitudinal study demonstrated.

The findings suggest that the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis may be affected in opposite directions by stress during pregnancy, Alison Shea, Ph.D. candidate, and her associates reported in a poster at the International Congress of Neuroendocrinology.

The analysis included 60 women who were among the first of 250 pregnant women to be recruited as part of the multicenter Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study led by Dr. Meir Steiner, of McMaster University, Hamilton, Ont.

The women were divided into three groups: those presenting with symptoms of depression or anxiety who chose psychotherapy only, those with symptoms who chose antidepressants, and a control group with no current or past psychiatric illness.

A battery of psychological tests was performed at baseline (gestational age 14–24 weeks), and morning salivary samples were collected daily to measure stress indicators such as cortisol, dehydroepiandrosterone (DHEA), and α-amylase. A follow-up assessment was performed at 24–30 weeks and included psychological testing, salivary samples, and a 24-hour Holter ECG.

Infants are being followed during the postpartum period until 3 years of age.

The results indicate that depression and anxiety scores during pregnancy are positively correlated with α-amylase levels and negatively correlated with morning cortisol levels.

Both associations were statistically significant, reported Ms. Shea, of the Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton.

Compared with controls, both the cortisol response to awakening and the 24-hour heart rate variability were lower for mothers with anxiety and depression, particularly among those not taking antidepressants. Reduced heart rate variability indicates the body's inability to respond to stress in a changing environment, and is thought to improve with the use of antidepressants, Ms. Shea said in an interview. Interestingly, the study found that the greater the gravida's heart rate variability, the longer the gestation. “It makes sense, but it's never been looked at in pregnant women,” she said.

Head circumference at birth was strongly correlated with maternal 24-hour mean heart rate during pregnancy, even after controlling for birth weight and gestational age.

Among women with depression and anxiety, the higher the heart rate during pregnancy, the smaller the head circumference. Head circumference is purported to be a measure of brain volume and has been found to be smaller among babies born to women with posttraumatic stress disorder, she said.

Birth length was significantly smaller for babies born to women with anxiety or depression (49.64 cm), compared with those born to women treated with antidepressants (50.91 cm) and controls (53.01 cm).

Ponderal index, which is an indicator of infant body mass index, also was significantly higher among babies of women suffering from anxiety and depression (2.65 g/cm

The data provide some insights into the mechanisms by which stress, depression, and anxiety impact fetal development. But Ms. Shea cautioned that the data remain preliminary and the number of patients is small.

PITTSBURGH — Pregnant women with anxiety or depression have higher levels of α-amylase, a measure of adrenergic system activity, and lower morning cortisol levels, preliminary results from a longitudinal study demonstrated.

The findings suggest that the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis may be affected in opposite directions by stress during pregnancy, Alison Shea, Ph.D. candidate, and her associates reported in a poster at the International Congress of Neuroendocrinology.

The analysis included 60 women who were among the first of 250 pregnant women to be recruited as part of the multicenter Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study led by Dr. Meir Steiner, of McMaster University, Hamilton, Ont.

The women were divided into three groups: those presenting with symptoms of depression or anxiety who chose psychotherapy only, those with symptoms who chose antidepressants, and a control group with no current or past psychiatric illness.

A battery of psychological tests was performed at baseline (gestational age 14–24 weeks), and morning salivary samples were collected daily to measure stress indicators such as cortisol, dehydroepiandrosterone (DHEA), and α-amylase. A follow-up assessment was performed at 24–30 weeks and included psychological testing, salivary samples, and a 24-hour Holter ECG.

Infants are being followed during the postpartum period until 3 years of age.

The results indicate that depression and anxiety scores during pregnancy are positively correlated with α-amylase levels and negatively correlated with morning cortisol levels.

Both associations were statistically significant, reported Ms. Shea, of the Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton.

Compared with controls, both the cortisol response to awakening and the 24-hour heart rate variability were lower for mothers with anxiety and depression, particularly among those not taking antidepressants. Reduced heart rate variability indicates the body's inability to respond to stress in a changing environment, and is thought to improve with the use of antidepressants, Ms. Shea said in an interview. Interestingly, the study found that the greater the gravida's heart rate variability, the longer the gestation. “It makes sense, but it's never been looked at in pregnant women,” she said.

Head circumference at birth was strongly correlated with maternal 24-hour mean heart rate during pregnancy, even after controlling for birth weight and gestational age.

Among women with depression and anxiety, the higher the heart rate during pregnancy, the smaller the head circumference. Head circumference is purported to be a measure of brain volume and has been found to be smaller among babies born to women with posttraumatic stress disorder, she said.

Birth length was significantly smaller for babies born to women with anxiety or depression (49.64 cm), compared with those born to women treated with antidepressants (50.91 cm) and controls (53.01 cm).

Ponderal index, which is an indicator of infant body mass index, also was significantly higher among babies of women suffering from anxiety and depression (2.65 g/cm

The data provide some insights into the mechanisms by which stress, depression, and anxiety impact fetal development. But Ms. Shea cautioned that the data remain preliminary and the number of patients is small.

PITTSBURGH — Pregnant women with anxiety or depression have higher levels of α-amylase, a measure of adrenergic system activity, and lower morning cortisol levels, preliminary results from a longitudinal study demonstrated.

The findings suggest that the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis may be affected in opposite directions by stress during pregnancy, Alison Shea, Ph.D. candidate, and her associates reported in a poster at the International Congress of Neuroendocrinology.

The analysis included 60 women who were among the first of 250 pregnant women to be recruited as part of the multicenter Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study led by Dr. Meir Steiner, of McMaster University, Hamilton, Ont.

The women were divided into three groups: those presenting with symptoms of depression or anxiety who chose psychotherapy only, those with symptoms who chose antidepressants, and a control group with no current or past psychiatric illness.

A battery of psychological tests was performed at baseline (gestational age 14–24 weeks), and morning salivary samples were collected daily to measure stress indicators such as cortisol, dehydroepiandrosterone (DHEA), and α-amylase. A follow-up assessment was performed at 24–30 weeks and included psychological testing, salivary samples, and a 24-hour Holter ECG.

Infants are being followed during the postpartum period until 3 years of age.

The results indicate that depression and anxiety scores during pregnancy are positively correlated with α-amylase levels and negatively correlated with morning cortisol levels.

Both associations were statistically significant, reported Ms. Shea, of the Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton.

Compared with controls, both the cortisol response to awakening and the 24-hour heart rate variability were lower for mothers with anxiety and depression, particularly among those not taking antidepressants. Reduced heart rate variability indicates the body's inability to respond to stress in a changing environment, and is thought to improve with the use of antidepressants, Ms. Shea said in an interview. Interestingly, the study found that the greater the gravida's heart rate variability, the longer the gestation. “It makes sense, but it's never been looked at in pregnant women,” she said.

Head circumference at birth was strongly correlated with maternal 24-hour mean heart rate during pregnancy, even after controlling for birth weight and gestational age.

Among women with depression and anxiety, the higher the heart rate during pregnancy, the smaller the head circumference. Head circumference is purported to be a measure of brain volume and has been found to be smaller among babies born to women with posttraumatic stress disorder, she said.

Birth length was significantly smaller for babies born to women with anxiety or depression (49.64 cm), compared with those born to women treated with antidepressants (50.91 cm) and controls (53.01 cm).

Ponderal index, which is an indicator of infant body mass index, also was significantly higher among babies of women suffering from anxiety and depression (2.65 g/cm

The data provide some insights into the mechanisms by which stress, depression, and anxiety impact fetal development. But Ms. Shea cautioned that the data remain preliminary and the number of patients is small.