Pulmonary Health Hub

The current pertussis epidemic in Washington state and increased rates nationwide underline the critical importance of vaccinating pregnant women and other adults who are in contact with babies against pertussis, Dr. Anne Schuchat said during a Centers for Disease Control and Prevention telebriefing.

Reports of pertussis have been increasing in infants, as well as among children aged 10, 13, and 14 years in Washington and nationwide, making the recommended booster for children with the Tdap vaccine essential, said Dr. Schuchat, director of the National Center for Immunization and Respiratory Diseases at the CDC in Atlanta.

Pertussis vaccination "remains the single most effective approach to preventing infection," she said, noting that unvaccinated children are at an eightfold greater risk of getting pertussis than those who have been fully vaccinated with DTaP. And vaccinated children who do contract pertussis typically have milder cases.

©CDC

In 2010, only 8% of adults had any history of having received a Tdap booster, she said.

In addition to encouraging patients to get the vaccine, clinicians also are being urged to consider pertussis as a possible diagnosis in their patients who have a persistent cough, she said.

Since the middle of 2011, cases of pertussis have been increasing in Washington state, and in April 2012, a pertussis epidemic was declared when 640 cases had been reported. As of June 16, 2,520 cases had been reported in 2012, a 1,300% increase from the same time period the year before, and the highest number of cases reported since the early 1940s (MMWR 2012;61:517-22).

To date, nine babies in the United States have died of whooping cough (one more than reported in the MMWR), Dr. Schuchat reported.

A higher-than-expected number of cases also have been reported in other states, with similar trends in the age groups affected, "and there may be many more coming," Dr. Schuchat said. In 2010, more than 27,000 cases were reported nationally, with 27 deaths (25 in infants).

Pertussis outbreaks occur in waves, with peaks every 3-5 years. During this current wave, the highest rates have been in infants under 1 year of age, with over half in babies under 3 months. These children are too young to be protected with the vaccine that is first administered at age 2 months, so they are dependent on the immunity of people around them, which is why pregnant women and adults who are around babies are being urged to get vaccinated, she said.

The rates of pertussis have started to increase after late childhood, with a higher rate in 10-year-olds, but then the rate decreases in 11- to 12-year-olds, and then increases among 13-year-olds, Dr. Schuchat said. These trends also point to the importance of the recommended Tdap vaccine in those aged 11 and 12 years .

The increase in pertussis cases reported in adolescents aged 13-14 in Washington state and nationally is a concern, and possible causes are being studied further. A contributing factor could be the switch from the whole cell to the acellular vaccine, which may have an effect on how long immunity persists. "Waning of protection over time may be part of the story," she said, pointing out that unvaccinated people are not thought to be driving this current wave of infection.

Dr. Schuchat said that the increase in pertussis cases goes beyond Washington State. "We really think the disease is spreading around the country. ...We’re in for a tough year and a tough couple of years."

The current pertussis epidemic in Washington state and increased rates nationwide underline the critical importance of vaccinating pregnant women and other adults who are in contact with babies against pertussis, Dr. Anne Schuchat said during a Centers for Disease Control and Prevention telebriefing.

Reports of pertussis have been increasing in infants, as well as among children aged 10, 13, and 14 years in Washington and nationwide, making the recommended booster for children with the Tdap vaccine essential, said Dr. Schuchat, director of the National Center for Immunization and Respiratory Diseases at the CDC in Atlanta.

Pertussis vaccination "remains the single most effective approach to preventing infection," she said, noting that unvaccinated children are at an eightfold greater risk of getting pertussis than those who have been fully vaccinated with DTaP. And vaccinated children who do contract pertussis typically have milder cases.

©CDC

In 2010, only 8% of adults had any history of having received a Tdap booster, she said.

In addition to encouraging patients to get the vaccine, clinicians also are being urged to consider pertussis as a possible diagnosis in their patients who have a persistent cough, she said.

Since the middle of 2011, cases of pertussis have been increasing in Washington state, and in April 2012, a pertussis epidemic was declared when 640 cases had been reported. As of June 16, 2,520 cases had been reported in 2012, a 1,300% increase from the same time period the year before, and the highest number of cases reported since the early 1940s (MMWR 2012;61:517-22).

To date, nine babies in the United States have died of whooping cough (one more than reported in the MMWR), Dr. Schuchat reported.

A higher-than-expected number of cases also have been reported in other states, with similar trends in the age groups affected, "and there may be many more coming," Dr. Schuchat said. In 2010, more than 27,000 cases were reported nationally, with 27 deaths (25 in infants).

Pertussis outbreaks occur in waves, with peaks every 3-5 years. During this current wave, the highest rates have been in infants under 1 year of age, with over half in babies under 3 months. These children are too young to be protected with the vaccine that is first administered at age 2 months, so they are dependent on the immunity of people around them, which is why pregnant women and adults who are around babies are being urged to get vaccinated, she said.

The rates of pertussis have started to increase after late childhood, with a higher rate in 10-year-olds, but then the rate decreases in 11- to 12-year-olds, and then increases among 13-year-olds, Dr. Schuchat said. These trends also point to the importance of the recommended Tdap vaccine in those aged 11 and 12 years .

The increase in pertussis cases reported in adolescents aged 13-14 in Washington state and nationally is a concern, and possible causes are being studied further. A contributing factor could be the switch from the whole cell to the acellular vaccine, which may have an effect on how long immunity persists. "Waning of protection over time may be part of the story," she said, pointing out that unvaccinated people are not thought to be driving this current wave of infection.

Dr. Schuchat said that the increase in pertussis cases goes beyond Washington State. "We really think the disease is spreading around the country. ...We’re in for a tough year and a tough couple of years."

The current pertussis epidemic in Washington state and increased rates nationwide underline the critical importance of vaccinating pregnant women and other adults who are in contact with babies against pertussis, Dr. Anne Schuchat said during a Centers for Disease Control and Prevention telebriefing.

Reports of pertussis have been increasing in infants, as well as among children aged 10, 13, and 14 years in Washington and nationwide, making the recommended booster for children with the Tdap vaccine essential, said Dr. Schuchat, director of the National Center for Immunization and Respiratory Diseases at the CDC in Atlanta.

Pertussis vaccination "remains the single most effective approach to preventing infection," she said, noting that unvaccinated children are at an eightfold greater risk of getting pertussis than those who have been fully vaccinated with DTaP. And vaccinated children who do contract pertussis typically have milder cases.

©CDC

In 2010, only 8% of adults had any history of having received a Tdap booster, she said.

In addition to encouraging patients to get the vaccine, clinicians also are being urged to consider pertussis as a possible diagnosis in their patients who have a persistent cough, she said.

Since the middle of 2011, cases of pertussis have been increasing in Washington state, and in April 2012, a pertussis epidemic was declared when 640 cases had been reported. As of June 16, 2,520 cases had been reported in 2012, a 1,300% increase from the same time period the year before, and the highest number of cases reported since the early 1940s (MMWR 2012;61:517-22).

To date, nine babies in the United States have died of whooping cough (one more than reported in the MMWR), Dr. Schuchat reported.

A higher-than-expected number of cases also have been reported in other states, with similar trends in the age groups affected, "and there may be many more coming," Dr. Schuchat said. In 2010, more than 27,000 cases were reported nationally, with 27 deaths (25 in infants).

Pertussis outbreaks occur in waves, with peaks every 3-5 years. During this current wave, the highest rates have been in infants under 1 year of age, with over half in babies under 3 months. These children are too young to be protected with the vaccine that is first administered at age 2 months, so they are dependent on the immunity of people around them, which is why pregnant women and adults who are around babies are being urged to get vaccinated, she said.

The rates of pertussis have started to increase after late childhood, with a higher rate in 10-year-olds, but then the rate decreases in 11- to 12-year-olds, and then increases among 13-year-olds, Dr. Schuchat said. These trends also point to the importance of the recommended Tdap vaccine in those aged 11 and 12 years .

The increase in pertussis cases reported in adolescents aged 13-14 in Washington state and nationally is a concern, and possible causes are being studied further. A contributing factor could be the switch from the whole cell to the acellular vaccine, which may have an effect on how long immunity persists. "Waning of protection over time may be part of the story," she said, pointing out that unvaccinated people are not thought to be driving this current wave of infection.

Dr. Schuchat said that the increase in pertussis cases goes beyond Washington State. "We really think the disease is spreading around the country. ...We’re in for a tough year and a tough couple of years."

Oral immunotherapy using egg-white powder represents a highly promising therapeutic intervention for children with egg allergy, according to findings from a randomized, placebo-controlled trial reported online in the July 19 issue of the New England Journal of Medicine.

After 10 months of immunotherapy, none of the 15 children with egg allergy who received placebo as part of the double-blind study passed an oral food challenge of 5 g of egg-white powder, whereas 22 (55%) of 40 children who received oral immunotherapy passed the oral food challenge and were considered to be desensitized. At 22 months, 30 (75%) of the 40 children who received oral immunotherapy passed an oral food challenge with 10 g of egg-white powder, Dr. A. Wesley Burks, chair of the department of pediatrics at the University of North Carolina and chief physician of N.C. Children’s Hospital, his colleagues reported on behalf of the Consortium of Food Allergy Research.

Photo © paci77/iStockphoto.com

Of the 30 children who passed the oral food challenge at 22 months, 29 were rechallenged at 24 months with 10 g of egg-white powder, followed 1 hour later with one whole cooked egg (after having discontinued immunotherapy and egg consumption for 4-6 weeks); 11 (28%) passed the challenge and were considered to have "sustained unresponsiveness," the investigators reported (N. Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1200435]).

These 11 children then were instructed to add egg to their diet ad libitum. No adverse events were reported at the 30- and 36-month follow-ups.

Study participants were children aged 5-18 years (median, 7 years) with a convincing clinical history of egg allergy and a serum egg-specific IgE antibody level of more than 5 kU/L for those aged 6 years and older, and 12 kU/L or more for those aged 5 years. Those with a history of severe anaphylaxis after egg consumption were excluded.

The protocol for oral immunotherapy consisted of an initial-day dose escalation, a build-up phase, and a maintenance phase involving ingestion of up to 2 g of egg-white powder (equivalent of about one-third of an egg) daily.

Factors that were found to be associated with sustained unresponsiveness at 24 months were higher egg-specific IgG4 antibody levels at 10 months, smaller wheal diameter on skin-prick allergy testing at 22 months, and a decrease in wheal size from baseline to 22 months, the investigators noted.

Oral immunotherapy in this study was generally well tolerated, with adverse events occurring most frequently in association with oral-immunotherapy dosing. Most of the events were mild (grade 1), with only 1% being graded as moderate (grade 2). No severe adverse events occurred. Most events were oral or pharyngeal, and were associated with 25% of the 11,860 doses of oral immunotherapy, and with 3.9% of the 4,018 doses of placebo. The rate of symptoms decreased to 8.3% of 15,815 doses in the oral immunotherapy group after 10 months.

The findings could have important implications, given that the cumulative prevalence of egg allergy is approximately 2.6% by 2.5 years of age, and that egg avoidance (which is difficult and can adversely affect quality of life) is the only available treatment for egg allergy, investigators said.

However, for oral immunotherapy to be recommended as a standard of care, it is important to better define risks, compared with allergen avoidance; to determine the dosing regimens with the most favorable outcomes; to identify the patients most likely to benefit; and to develop postdesensitization strategies, the investigators concluded.

This study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health–National Center for Research Resources Clinical Translational Science Awards and Clinical Research Centers. Dr. A. Wesley Burks has been a consultant for companies including Dannon Co. Probiotic, McNeil Nutritionals, Merck, the Food Allergy & Anaphylaxis Network, and Novartis, and has grants or grants pending from the Food Allergy Initiative, the NIH, the National Peanut Board, and others. Some of his associates were consultants for companies including DBV Technologies, Allertein Therapeutics, and Sunovion, or received grants from various companies; other associates had no relevant financial disclosures.

CLARIFICATION 7/20/2012: The institutional affiliation of Dr. Burks has been updated to reflect his current position.

Oral immunotherapy using egg-white powder represents a highly promising therapeutic intervention for children with egg allergy, according to findings from a randomized, placebo-controlled trial reported online in the July 19 issue of the New England Journal of Medicine.

After 10 months of immunotherapy, none of the 15 children with egg allergy who received placebo as part of the double-blind study passed an oral food challenge of 5 g of egg-white powder, whereas 22 (55%) of 40 children who received oral immunotherapy passed the oral food challenge and were considered to be desensitized. At 22 months, 30 (75%) of the 40 children who received oral immunotherapy passed an oral food challenge with 10 g of egg-white powder, Dr. A. Wesley Burks, chair of the department of pediatrics at the University of North Carolina and chief physician of N.C. Children’s Hospital, his colleagues reported on behalf of the Consortium of Food Allergy Research.

Photo © paci77/iStockphoto.com

Of the 30 children who passed the oral food challenge at 22 months, 29 were rechallenged at 24 months with 10 g of egg-white powder, followed 1 hour later with one whole cooked egg (after having discontinued immunotherapy and egg consumption for 4-6 weeks); 11 (28%) passed the challenge and were considered to have "sustained unresponsiveness," the investigators reported (N. Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1200435]).

These 11 children then were instructed to add egg to their diet ad libitum. No adverse events were reported at the 30- and 36-month follow-ups.

Study participants were children aged 5-18 years (median, 7 years) with a convincing clinical history of egg allergy and a serum egg-specific IgE antibody level of more than 5 kU/L for those aged 6 years and older, and 12 kU/L or more for those aged 5 years. Those with a history of severe anaphylaxis after egg consumption were excluded.

The protocol for oral immunotherapy consisted of an initial-day dose escalation, a build-up phase, and a maintenance phase involving ingestion of up to 2 g of egg-white powder (equivalent of about one-third of an egg) daily.

Factors that were found to be associated with sustained unresponsiveness at 24 months were higher egg-specific IgG4 antibody levels at 10 months, smaller wheal diameter on skin-prick allergy testing at 22 months, and a decrease in wheal size from baseline to 22 months, the investigators noted.

Oral immunotherapy in this study was generally well tolerated, with adverse events occurring most frequently in association with oral-immunotherapy dosing. Most of the events were mild (grade 1), with only 1% being graded as moderate (grade 2). No severe adverse events occurred. Most events were oral or pharyngeal, and were associated with 25% of the 11,860 doses of oral immunotherapy, and with 3.9% of the 4,018 doses of placebo. The rate of symptoms decreased to 8.3% of 15,815 doses in the oral immunotherapy group after 10 months.

The findings could have important implications, given that the cumulative prevalence of egg allergy is approximately 2.6% by 2.5 years of age, and that egg avoidance (which is difficult and can adversely affect quality of life) is the only available treatment for egg allergy, investigators said.

However, for oral immunotherapy to be recommended as a standard of care, it is important to better define risks, compared with allergen avoidance; to determine the dosing regimens with the most favorable outcomes; to identify the patients most likely to benefit; and to develop postdesensitization strategies, the investigators concluded.

This study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health–National Center for Research Resources Clinical Translational Science Awards and Clinical Research Centers. Dr. A. Wesley Burks has been a consultant for companies including Dannon Co. Probiotic, McNeil Nutritionals, Merck, the Food Allergy & Anaphylaxis Network, and Novartis, and has grants or grants pending from the Food Allergy Initiative, the NIH, the National Peanut Board, and others. Some of his associates were consultants for companies including DBV Technologies, Allertein Therapeutics, and Sunovion, or received grants from various companies; other associates had no relevant financial disclosures.

CLARIFICATION 7/20/2012: The institutional affiliation of Dr. Burks has been updated to reflect his current position.

Oral immunotherapy using egg-white powder represents a highly promising therapeutic intervention for children with egg allergy, according to findings from a randomized, placebo-controlled trial reported online in the July 19 issue of the New England Journal of Medicine.

After 10 months of immunotherapy, none of the 15 children with egg allergy who received placebo as part of the double-blind study passed an oral food challenge of 5 g of egg-white powder, whereas 22 (55%) of 40 children who received oral immunotherapy passed the oral food challenge and were considered to be desensitized. At 22 months, 30 (75%) of the 40 children who received oral immunotherapy passed an oral food challenge with 10 g of egg-white powder, Dr. A. Wesley Burks, chair of the department of pediatrics at the University of North Carolina and chief physician of N.C. Children’s Hospital, his colleagues reported on behalf of the Consortium of Food Allergy Research.

Photo © paci77/iStockphoto.com

Of the 30 children who passed the oral food challenge at 22 months, 29 were rechallenged at 24 months with 10 g of egg-white powder, followed 1 hour later with one whole cooked egg (after having discontinued immunotherapy and egg consumption for 4-6 weeks); 11 (28%) passed the challenge and were considered to have "sustained unresponsiveness," the investigators reported (N. Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1200435]).

These 11 children then were instructed to add egg to their diet ad libitum. No adverse events were reported at the 30- and 36-month follow-ups.

Study participants were children aged 5-18 years (median, 7 years) with a convincing clinical history of egg allergy and a serum egg-specific IgE antibody level of more than 5 kU/L for those aged 6 years and older, and 12 kU/L or more for those aged 5 years. Those with a history of severe anaphylaxis after egg consumption were excluded.

The protocol for oral immunotherapy consisted of an initial-day dose escalation, a build-up phase, and a maintenance phase involving ingestion of up to 2 g of egg-white powder (equivalent of about one-third of an egg) daily.

Factors that were found to be associated with sustained unresponsiveness at 24 months were higher egg-specific IgG4 antibody levels at 10 months, smaller wheal diameter on skin-prick allergy testing at 22 months, and a decrease in wheal size from baseline to 22 months, the investigators noted.

Oral immunotherapy in this study was generally well tolerated, with adverse events occurring most frequently in association with oral-immunotherapy dosing. Most of the events were mild (grade 1), with only 1% being graded as moderate (grade 2). No severe adverse events occurred. Most events were oral or pharyngeal, and were associated with 25% of the 11,860 doses of oral immunotherapy, and with 3.9% of the 4,018 doses of placebo. The rate of symptoms decreased to 8.3% of 15,815 doses in the oral immunotherapy group after 10 months.

The findings could have important implications, given that the cumulative prevalence of egg allergy is approximately 2.6% by 2.5 years of age, and that egg avoidance (which is difficult and can adversely affect quality of life) is the only available treatment for egg allergy, investigators said.

However, for oral immunotherapy to be recommended as a standard of care, it is important to better define risks, compared with allergen avoidance; to determine the dosing regimens with the most favorable outcomes; to identify the patients most likely to benefit; and to develop postdesensitization strategies, the investigators concluded.

This study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health–National Center for Research Resources Clinical Translational Science Awards and Clinical Research Centers. Dr. A. Wesley Burks has been a consultant for companies including Dannon Co. Probiotic, McNeil Nutritionals, Merck, the Food Allergy & Anaphylaxis Network, and Novartis, and has grants or grants pending from the Food Allergy Initiative, the NIH, the National Peanut Board, and others. Some of his associates were consultants for companies including DBV Technologies, Allertein Therapeutics, and Sunovion, or received grants from various companies; other associates had no relevant financial disclosures.

CLARIFICATION 7/20/2012: The institutional affiliation of Dr. Burks has been updated to reflect his current position.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

SAN DIEGO – Measuring the number of oxygen desaturations a patient has that are coincident with episodes of esophageal acidity may be an effective new way to identify patients who primarily have respiratory symptoms secondary to gastroesophageal reflux, based on results from a controlled study involving 103 people.

"These data provide further proof of principle that reflux-associated oxygen desaturations are more common in GERD [gastroesophageal reflux disease] patients with respiratory complaints, and may be a useful discriminatory test in GERD patients with primarily respiratory symptoms," Dr. Candice L. Wilshire said at the annual Digestive Disease Week.

"We believe that the desaturations are due to reflux, and we think that if you stop the reflux with surgery you should cure it," said Dr. Wilshire, a thoracic surgeon at the University of Rochester (N.Y.). "We believe that looking at the reflux-associated desaturations could identify patients who have pulmonary symptoms due to reflux, as opposed to primarily pulmonary pathology."

But Dr. Wilshire cautioned that counting a patient’s reflux-associated oxygen desaturations is not ready for routine diagnostic use. "Currently, our indications for [antireflux] surgery have not changed," she said. "At the moment, we use a separate esophageal pH catheter and pulse oximeter, and there are some artifacts," which means that this assessment method is still in development, Dr. Wilshire said in an interview. Further research is needed to "discern what are true desaturations" caused by reflux and "what are artifacts. It would be nice to get some software that can do this for us. I think there are things we could do to make [these assessments] easier and to eliminate some of the artifacts."

Having a reliable way to identify patients who experience frequent oxygen desaturation episodes that are secondary to reflux should refine diagnoses and streamline delivery of appropriate treatment to patients, Dr. Wilshire said. "A subgroup of GERD patients have no gastrointestinal symptoms and just complain of a chronic cough. They get sent to us when they’re far down the road, after seeing pulmonologists." Her new approach for identifying the pulmonary consequences of GERD – by counting episodes of oxygen desaturation – may provide a way to more quickly identify these types of patients, she said.

Her study enrolled 37 GERD patients who primarily had respiratory symptoms (cough, hoarseness, or throat clearing), 26 GERD patients who primarily had gastrointestinal symptoms (such as heartburn or epigastric pain), and 40 controls who were asymptomatic.

All participants underwent 24-hour, ambulatory assessment with a pair of measurement devices: a finger-clip device for measuring oxygen saturation, and a multichannel, intraluminal pH impedance monitor to measure esophageal pH. The researchers tallied an oxygen desaturation episode whenever the subject’s blood oxygen level dropped below 90% or at least 6 percentage points below the person’s baseline level. They tallied acid-reflux episodes as times when esophageal pH registered less than 4, in both proximal and distal sites of the esophagus. They considered reflux-associated oxygen desaturations (RADs) to be desaturations that occurred within 5 minutes of a reflux episode.

The results showed that the controls had a median of 3.0 distal RADs during 24 hours, and the 95th percentile number was 11.0 RADs. In comparison, the patients with GERD and gastrointestinal symptoms had a median of 6.5 RADs, significantly more than the controls; the patients with GERD and pulmonary symptoms had a median of 17.0 RADs, significantly more than both the control group and those with gastrointestinal GERD.

The researchers found a similar pattern for proximal acid-episode RADs. The control group had a median of 1.0 episode during 24 hours, with a 95th percentile level of 7.0 episodes. Patients with gastrointestinal GERD symptoms had a median of 3.0 RADs, significantly more than the controls, whereas those with primarily pulmonary symptoms of GERD had a median of 8.0 RADs, significantly more than the controls and the patients with primarily gastrointestinal symptoms.

The percentage of patients with 11 or more distal RADs – the "elevated" threshold, based on the benchmark established by the controls – was 27% in patients with primarily gastrointestinal symptoms of GERD and 70% in those with primarily pulmonary symptoms of GERD. The percentage with an elevated number of proximal RADs (more than 7) was 19% in the gastrointestinal group and 62% in the pulmonary group, Dr. Wilshire reported.

In addition, RAD numbers substantially declined in the small number of patients in the study who had their symptoms improve by undergoing antireflux surgery and who had their RADs measured before and after surgery.

Dr. Wilshire said that she had no disclosures.

SAN DIEGO – Measuring the number of oxygen desaturations a patient has that are coincident with episodes of esophageal acidity may be an effective new way to identify patients who primarily have respiratory symptoms secondary to gastroesophageal reflux, based on results from a controlled study involving 103 people.

"These data provide further proof of principle that reflux-associated oxygen desaturations are more common in GERD [gastroesophageal reflux disease] patients with respiratory complaints, and may be a useful discriminatory test in GERD patients with primarily respiratory symptoms," Dr. Candice L. Wilshire said at the annual Digestive Disease Week.

"We believe that the desaturations are due to reflux, and we think that if you stop the reflux with surgery you should cure it," said Dr. Wilshire, a thoracic surgeon at the University of Rochester (N.Y.). "We believe that looking at the reflux-associated desaturations could identify patients who have pulmonary symptoms due to reflux, as opposed to primarily pulmonary pathology."

But Dr. Wilshire cautioned that counting a patient’s reflux-associated oxygen desaturations is not ready for routine diagnostic use. "Currently, our indications for [antireflux] surgery have not changed," she said. "At the moment, we use a separate esophageal pH catheter and pulse oximeter, and there are some artifacts," which means that this assessment method is still in development, Dr. Wilshire said in an interview. Further research is needed to "discern what are true desaturations" caused by reflux and "what are artifacts. It would be nice to get some software that can do this for us. I think there are things we could do to make [these assessments] easier and to eliminate some of the artifacts."

Having a reliable way to identify patients who experience frequent oxygen desaturation episodes that are secondary to reflux should refine diagnoses and streamline delivery of appropriate treatment to patients, Dr. Wilshire said. "A subgroup of GERD patients have no gastrointestinal symptoms and just complain of a chronic cough. They get sent to us when they’re far down the road, after seeing pulmonologists." Her new approach for identifying the pulmonary consequences of GERD – by counting episodes of oxygen desaturation – may provide a way to more quickly identify these types of patients, she said.

Her study enrolled 37 GERD patients who primarily had respiratory symptoms (cough, hoarseness, or throat clearing), 26 GERD patients who primarily had gastrointestinal symptoms (such as heartburn or epigastric pain), and 40 controls who were asymptomatic.

All participants underwent 24-hour, ambulatory assessment with a pair of measurement devices: a finger-clip device for measuring oxygen saturation, and a multichannel, intraluminal pH impedance monitor to measure esophageal pH. The researchers tallied an oxygen desaturation episode whenever the subject’s blood oxygen level dropped below 90% or at least 6 percentage points below the person’s baseline level. They tallied acid-reflux episodes as times when esophageal pH registered less than 4, in both proximal and distal sites of the esophagus. They considered reflux-associated oxygen desaturations (RADs) to be desaturations that occurred within 5 minutes of a reflux episode.

The results showed that the controls had a median of 3.0 distal RADs during 24 hours, and the 95th percentile number was 11.0 RADs. In comparison, the patients with GERD and gastrointestinal symptoms had a median of 6.5 RADs, significantly more than the controls; the patients with GERD and pulmonary symptoms had a median of 17.0 RADs, significantly more than both the control group and those with gastrointestinal GERD.

The researchers found a similar pattern for proximal acid-episode RADs. The control group had a median of 1.0 episode during 24 hours, with a 95th percentile level of 7.0 episodes. Patients with gastrointestinal GERD symptoms had a median of 3.0 RADs, significantly more than the controls, whereas those with primarily pulmonary symptoms of GERD had a median of 8.0 RADs, significantly more than the controls and the patients with primarily gastrointestinal symptoms.

The percentage of patients with 11 or more distal RADs – the "elevated" threshold, based on the benchmark established by the controls – was 27% in patients with primarily gastrointestinal symptoms of GERD and 70% in those with primarily pulmonary symptoms of GERD. The percentage with an elevated number of proximal RADs (more than 7) was 19% in the gastrointestinal group and 62% in the pulmonary group, Dr. Wilshire reported.

In addition, RAD numbers substantially declined in the small number of patients in the study who had their symptoms improve by undergoing antireflux surgery and who had their RADs measured before and after surgery.

Dr. Wilshire said that she had no disclosures.

SAN DIEGO – Measuring the number of oxygen desaturations a patient has that are coincident with episodes of esophageal acidity may be an effective new way to identify patients who primarily have respiratory symptoms secondary to gastroesophageal reflux, based on results from a controlled study involving 103 people.

"These data provide further proof of principle that reflux-associated oxygen desaturations are more common in GERD [gastroesophageal reflux disease] patients with respiratory complaints, and may be a useful discriminatory test in GERD patients with primarily respiratory symptoms," Dr. Candice L. Wilshire said at the annual Digestive Disease Week.

"We believe that the desaturations are due to reflux, and we think that if you stop the reflux with surgery you should cure it," said Dr. Wilshire, a thoracic surgeon at the University of Rochester (N.Y.). "We believe that looking at the reflux-associated desaturations could identify patients who have pulmonary symptoms due to reflux, as opposed to primarily pulmonary pathology."

But Dr. Wilshire cautioned that counting a patient’s reflux-associated oxygen desaturations is not ready for routine diagnostic use. "Currently, our indications for [antireflux] surgery have not changed," she said. "At the moment, we use a separate esophageal pH catheter and pulse oximeter, and there are some artifacts," which means that this assessment method is still in development, Dr. Wilshire said in an interview. Further research is needed to "discern what are true desaturations" caused by reflux and "what are artifacts. It would be nice to get some software that can do this for us. I think there are things we could do to make [these assessments] easier and to eliminate some of the artifacts."

Having a reliable way to identify patients who experience frequent oxygen desaturation episodes that are secondary to reflux should refine diagnoses and streamline delivery of appropriate treatment to patients, Dr. Wilshire said. "A subgroup of GERD patients have no gastrointestinal symptoms and just complain of a chronic cough. They get sent to us when they’re far down the road, after seeing pulmonologists." Her new approach for identifying the pulmonary consequences of GERD – by counting episodes of oxygen desaturation – may provide a way to more quickly identify these types of patients, she said.

Her study enrolled 37 GERD patients who primarily had respiratory symptoms (cough, hoarseness, or throat clearing), 26 GERD patients who primarily had gastrointestinal symptoms (such as heartburn or epigastric pain), and 40 controls who were asymptomatic.

All participants underwent 24-hour, ambulatory assessment with a pair of measurement devices: a finger-clip device for measuring oxygen saturation, and a multichannel, intraluminal pH impedance monitor to measure esophageal pH. The researchers tallied an oxygen desaturation episode whenever the subject’s blood oxygen level dropped below 90% or at least 6 percentage points below the person’s baseline level. They tallied acid-reflux episodes as times when esophageal pH registered less than 4, in both proximal and distal sites of the esophagus. They considered reflux-associated oxygen desaturations (RADs) to be desaturations that occurred within 5 minutes of a reflux episode.

The results showed that the controls had a median of 3.0 distal RADs during 24 hours, and the 95th percentile number was 11.0 RADs. In comparison, the patients with GERD and gastrointestinal symptoms had a median of 6.5 RADs, significantly more than the controls; the patients with GERD and pulmonary symptoms had a median of 17.0 RADs, significantly more than both the control group and those with gastrointestinal GERD.

The researchers found a similar pattern for proximal acid-episode RADs. The control group had a median of 1.0 episode during 24 hours, with a 95th percentile level of 7.0 episodes. Patients with gastrointestinal GERD symptoms had a median of 3.0 RADs, significantly more than the controls, whereas those with primarily pulmonary symptoms of GERD had a median of 8.0 RADs, significantly more than the controls and the patients with primarily gastrointestinal symptoms.

The percentage of patients with 11 or more distal RADs – the "elevated" threshold, based on the benchmark established by the controls – was 27% in patients with primarily gastrointestinal symptoms of GERD and 70% in those with primarily pulmonary symptoms of GERD. The percentage with an elevated number of proximal RADs (more than 7) was 19% in the gastrointestinal group and 62% in the pulmonary group, Dr. Wilshire reported.

In addition, RAD numbers substantially declined in the small number of patients in the study who had their symptoms improve by undergoing antireflux surgery and who had their RADs measured before and after surgery.

Dr. Wilshire said that she had no disclosures.

SAN FRANCISCO – Children aged 12 years and older may be less likely to have asthma exacerbations than are younger children, according a 44-week trial in 288 children with mild, persistent asthma.

Girls also may be less likely to have asthma exacerbations than are boys. The lower risk in girls and older children means that these patients probably don’t need inhaled corticosteroids (ICS) daily, but only for symptoms or rescue, said Dr. Joseph Gerald of the University of Arizona, Tucson.

"It’s a reasonable" approach that limits impaired growth and other potential ICS side effects when "the benefit to be gained from daily inhaled steroids is not that great," he said at an international conference of the American Thoracic Society.

The researchers randomized 72 children to daily ICS, 71 to rescue ICS only, 71 to combined treatment with ICS and inhaled albuterol, and 74 to placebo. The daily ICS regimen consisted of one 40-mcg puff of beclomethasone twice daily; combined treatment consisted of one 40-mcg puff of beclomethasone with each albuterol puff used for symptom relief. Dummy inhalers were used as needed to maintain blinding. The participants were 6-18 years old.

Compared with placebo, all three ICS regimens reduced treatment failures (defined as more than two exacerbations requiring oral corticosteroids) in boys, in children 6-11 years old, and in children with allergic forms of the disease as indicated by eczema, positive skin tests, methacholine PC₂₀ (a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) at or below 12.5 mg/dL, and IgE levels at or above 185 kU/L. For instance, 29.3% of boys (12 of 41) in the placebo group failed treatment, but only 2.4% of boys (1 of 42) in the daily ICS group did so.

The investigators were unable to show a statistically significant benefit for any ICS strategy in girls, in children 12-18 years old, and in those with higher methacholine PC₂₀ levels, lower IgE levels, negative skin tests, and no eczema.

That’s probably not because inhaled steroids work better in boys and other responders, but rather because nonresponders had lower exacerbation rates in general, making it harder to detect a benefit, Dr. Gerald said.

For example, although almost 30% of boys in the placebo group failed treatment, only 15.2% of girls (5 of 33) in the placebo group failed. Similarly, 26% of children aged 6-11 years (13 of 50) failed treatment in the placebo arm, but only 16.7% of children aged 12-18 years (4 of 24) did so.

"We think the baseline [exacerbation] risk is what we are detecting here. [Nonresponders] started from a lower risk and just didn’t benefit as much," Dr. Gerald said. The study did not determine the best ICS regimen among responders.

Dr. Gerald and his coinvestigators said they have no relevant disclosures.

SAN FRANCISCO – Children aged 12 years and older may be less likely to have asthma exacerbations than are younger children, according a 44-week trial in 288 children with mild, persistent asthma.

Girls also may be less likely to have asthma exacerbations than are boys. The lower risk in girls and older children means that these patients probably don’t need inhaled corticosteroids (ICS) daily, but only for symptoms or rescue, said Dr. Joseph Gerald of the University of Arizona, Tucson.

"It’s a reasonable" approach that limits impaired growth and other potential ICS side effects when "the benefit to be gained from daily inhaled steroids is not that great," he said at an international conference of the American Thoracic Society.

The researchers randomized 72 children to daily ICS, 71 to rescue ICS only, 71 to combined treatment with ICS and inhaled albuterol, and 74 to placebo. The daily ICS regimen consisted of one 40-mcg puff of beclomethasone twice daily; combined treatment consisted of one 40-mcg puff of beclomethasone with each albuterol puff used for symptom relief. Dummy inhalers were used as needed to maintain blinding. The participants were 6-18 years old.

Compared with placebo, all three ICS regimens reduced treatment failures (defined as more than two exacerbations requiring oral corticosteroids) in boys, in children 6-11 years old, and in children with allergic forms of the disease as indicated by eczema, positive skin tests, methacholine PC₂₀ (a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) at or below 12.5 mg/dL, and IgE levels at or above 185 kU/L. For instance, 29.3% of boys (12 of 41) in the placebo group failed treatment, but only 2.4% of boys (1 of 42) in the daily ICS group did so.

The investigators were unable to show a statistically significant benefit for any ICS strategy in girls, in children 12-18 years old, and in those with higher methacholine PC₂₀ levels, lower IgE levels, negative skin tests, and no eczema.

That’s probably not because inhaled steroids work better in boys and other responders, but rather because nonresponders had lower exacerbation rates in general, making it harder to detect a benefit, Dr. Gerald said.

For example, although almost 30% of boys in the placebo group failed treatment, only 15.2% of girls (5 of 33) in the placebo group failed. Similarly, 26% of children aged 6-11 years (13 of 50) failed treatment in the placebo arm, but only 16.7% of children aged 12-18 years (4 of 24) did so.

"We think the baseline [exacerbation] risk is what we are detecting here. [Nonresponders] started from a lower risk and just didn’t benefit as much," Dr. Gerald said. The study did not determine the best ICS regimen among responders.

Dr. Gerald and his coinvestigators said they have no relevant disclosures.

SAN FRANCISCO – Children aged 12 years and older may be less likely to have asthma exacerbations than are younger children, according a 44-week trial in 288 children with mild, persistent asthma.

Girls also may be less likely to have asthma exacerbations than are boys. The lower risk in girls and older children means that these patients probably don’t need inhaled corticosteroids (ICS) daily, but only for symptoms or rescue, said Dr. Joseph Gerald of the University of Arizona, Tucson.

"It’s a reasonable" approach that limits impaired growth and other potential ICS side effects when "the benefit to be gained from daily inhaled steroids is not that great," he said at an international conference of the American Thoracic Society.

The researchers randomized 72 children to daily ICS, 71 to rescue ICS only, 71 to combined treatment with ICS and inhaled albuterol, and 74 to placebo. The daily ICS regimen consisted of one 40-mcg puff of beclomethasone twice daily; combined treatment consisted of one 40-mcg puff of beclomethasone with each albuterol puff used for symptom relief. Dummy inhalers were used as needed to maintain blinding. The participants were 6-18 years old.

Compared with placebo, all three ICS regimens reduced treatment failures (defined as more than two exacerbations requiring oral corticosteroids) in boys, in children 6-11 years old, and in children with allergic forms of the disease as indicated by eczema, positive skin tests, methacholine PC₂₀ (a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) at or below 12.5 mg/dL, and IgE levels at or above 185 kU/L. For instance, 29.3% of boys (12 of 41) in the placebo group failed treatment, but only 2.4% of boys (1 of 42) in the daily ICS group did so.

The investigators were unable to show a statistically significant benefit for any ICS strategy in girls, in children 12-18 years old, and in those with higher methacholine PC₂₀ levels, lower IgE levels, negative skin tests, and no eczema.

That’s probably not because inhaled steroids work better in boys and other responders, but rather because nonresponders had lower exacerbation rates in general, making it harder to detect a benefit, Dr. Gerald said.

For example, although almost 30% of boys in the placebo group failed treatment, only 15.2% of girls (5 of 33) in the placebo group failed. Similarly, 26% of children aged 6-11 years (13 of 50) failed treatment in the placebo arm, but only 16.7% of children aged 12-18 years (4 of 24) did so.

"We think the baseline [exacerbation] risk is what we are detecting here. [Nonresponders] started from a lower risk and just didn’t benefit as much," Dr. Gerald said. The study did not determine the best ICS regimen among responders.

Dr. Gerald and his coinvestigators said they have no relevant disclosures.

BOSTON – Treatment with continuous positive airway pressure does double duty in patients with obstructive sleep apnea by improving their mood while promoting restful sleep, Dr. Charles Bae reported at the annual meeting of the Associated Professional Sleep Societies.

In a retrospective study of 769 adults with OSA, the Cleveland Clinic neurologist and his colleagues observed a significant decrease in depressive symptoms as measured by the Patient Health Questionnaire 9 (PHQ-9) among patients who used a CPAP device.

"A number of studies have confirmed an association between obstructive sleep apnea and depressive symptoms, but until now none have looked specifically at the link between CPAP and symptom severity as measured by PHQ-9," Dr. Bae said in an interview. "Our goal was to assess the impact of CPAP therapy on patient mood by measuring the change in depressive symptoms following treatment."

Toward this end, the investigators reviewed data for all of the adult patients (18 years or older) with OSA seen at the Cleveland Clinic Sleep Disorders Center from January 2008 to July 2011. Patients who met study criteria had been treated with CPAP and had at least two outpatient visits (one before and one within 30 days after initiating CPAP), had completed the PHQ-9 questionnaire, and had a pre-CPAP score on the questionnaire of at least 5, Dr. Bae said.

Of the 769 study patients (mean age, 51.8 years), 654 were characterized as adherent to CPAP therapy based on self-reported use of the device 4 or more hours per night; the remaining 115 used the device either inconsistently or for fewer than 4 hours per night and were considered nonadherent. The baseline PHQ-9 scores for patients in the adherent and nonadherent groups were similar, at 11.2 and 11.8, respectively. Significant decreases from baseline in PHQ-9 scores were observed in both groups, but the difference was "significantly more robust" in the adherent group at 3.8, compared with 2.0 in the nonadherent group, Dr. Bae reported.

The results were even more robust among patients who had reported sleepiness at baseline, according to Dr. Bae. Specifically, in the patients who had a minimum score of 10 on the Epworth Sleepiness Scale prior to CPAP, ESS scores decreased by 4.0 in the adherent group vs. 2.8 in the nonadherent group, he said. In the CPAP-adherent group, there was a significant difference between sleepy vs. nonsleepy patients in their average decrease in PHQ-9 score. "The PHQ-9 score dropped 4.3 points among patients whose [ESS] score was at least 10 at baseline, compared with 3.1 points among those whose score was less than 10," he said.

Marital status was also examined as a covariate in the multiple regression model and appeared to have an effect. The mean PHQ-9 score decrease among the 475 married patients after CPAP was 4.0, compared with 3.0 among single patients and 2.3 among divorced patients, Dr. Bae said, noting that the difference between married and divorced patients was significant.

While the specific mechanisms contributing to the mood improvements associated with CPAP treatment in OSA patients can’t be ascertained from a retrospective study, the findings are fairly intuitive, according to Dr. Bae. When people sleep better, "a lot of things look better," he said.

Dr. Bae disclosed no relevant conflicts of interest.

BOSTON – Treatment with continuous positive airway pressure does double duty in patients with obstructive sleep apnea by improving their mood while promoting restful sleep, Dr. Charles Bae reported at the annual meeting of the Associated Professional Sleep Societies.

In a retrospective study of 769 adults with OSA, the Cleveland Clinic neurologist and his colleagues observed a significant decrease in depressive symptoms as measured by the Patient Health Questionnaire 9 (PHQ-9) among patients who used a CPAP device.

"A number of studies have confirmed an association between obstructive sleep apnea and depressive symptoms, but until now none have looked specifically at the link between CPAP and symptom severity as measured by PHQ-9," Dr. Bae said in an interview. "Our goal was to assess the impact of CPAP therapy on patient mood by measuring the change in depressive symptoms following treatment."

Toward this end, the investigators reviewed data for all of the adult patients (18 years or older) with OSA seen at the Cleveland Clinic Sleep Disorders Center from January 2008 to July 2011. Patients who met study criteria had been treated with CPAP and had at least two outpatient visits (one before and one within 30 days after initiating CPAP), had completed the PHQ-9 questionnaire, and had a pre-CPAP score on the questionnaire of at least 5, Dr. Bae said.

Of the 769 study patients (mean age, 51.8 years), 654 were characterized as adherent to CPAP therapy based on self-reported use of the device 4 or more hours per night; the remaining 115 used the device either inconsistently or for fewer than 4 hours per night and were considered nonadherent. The baseline PHQ-9 scores for patients in the adherent and nonadherent groups were similar, at 11.2 and 11.8, respectively. Significant decreases from baseline in PHQ-9 scores were observed in both groups, but the difference was "significantly more robust" in the adherent group at 3.8, compared with 2.0 in the nonadherent group, Dr. Bae reported.

The results were even more robust among patients who had reported sleepiness at baseline, according to Dr. Bae. Specifically, in the patients who had a minimum score of 10 on the Epworth Sleepiness Scale prior to CPAP, ESS scores decreased by 4.0 in the adherent group vs. 2.8 in the nonadherent group, he said. In the CPAP-adherent group, there was a significant difference between sleepy vs. nonsleepy patients in their average decrease in PHQ-9 score. "The PHQ-9 score dropped 4.3 points among patients whose [ESS] score was at least 10 at baseline, compared with 3.1 points among those whose score was less than 10," he said.

Marital status was also examined as a covariate in the multiple regression model and appeared to have an effect. The mean PHQ-9 score decrease among the 475 married patients after CPAP was 4.0, compared with 3.0 among single patients and 2.3 among divorced patients, Dr. Bae said, noting that the difference between married and divorced patients was significant.

While the specific mechanisms contributing to the mood improvements associated with CPAP treatment in OSA patients can’t be ascertained from a retrospective study, the findings are fairly intuitive, according to Dr. Bae. When people sleep better, "a lot of things look better," he said.

Dr. Bae disclosed no relevant conflicts of interest.

BOSTON – Treatment with continuous positive airway pressure does double duty in patients with obstructive sleep apnea by improving their mood while promoting restful sleep, Dr. Charles Bae reported at the annual meeting of the Associated Professional Sleep Societies.

In a retrospective study of 769 adults with OSA, the Cleveland Clinic neurologist and his colleagues observed a significant decrease in depressive symptoms as measured by the Patient Health Questionnaire 9 (PHQ-9) among patients who used a CPAP device.

"A number of studies have confirmed an association between obstructive sleep apnea and depressive symptoms, but until now none have looked specifically at the link between CPAP and symptom severity as measured by PHQ-9," Dr. Bae said in an interview. "Our goal was to assess the impact of CPAP therapy on patient mood by measuring the change in depressive symptoms following treatment."

Toward this end, the investigators reviewed data for all of the adult patients (18 years or older) with OSA seen at the Cleveland Clinic Sleep Disorders Center from January 2008 to July 2011. Patients who met study criteria had been treated with CPAP and had at least two outpatient visits (one before and one within 30 days after initiating CPAP), had completed the PHQ-9 questionnaire, and had a pre-CPAP score on the questionnaire of at least 5, Dr. Bae said.

Of the 769 study patients (mean age, 51.8 years), 654 were characterized as adherent to CPAP therapy based on self-reported use of the device 4 or more hours per night; the remaining 115 used the device either inconsistently or for fewer than 4 hours per night and were considered nonadherent. The baseline PHQ-9 scores for patients in the adherent and nonadherent groups were similar, at 11.2 and 11.8, respectively. Significant decreases from baseline in PHQ-9 scores were observed in both groups, but the difference was "significantly more robust" in the adherent group at 3.8, compared with 2.0 in the nonadherent group, Dr. Bae reported.

The results were even more robust among patients who had reported sleepiness at baseline, according to Dr. Bae. Specifically, in the patients who had a minimum score of 10 on the Epworth Sleepiness Scale prior to CPAP, ESS scores decreased by 4.0 in the adherent group vs. 2.8 in the nonadherent group, he said. In the CPAP-adherent group, there was a significant difference between sleepy vs. nonsleepy patients in their average decrease in PHQ-9 score. "The PHQ-9 score dropped 4.3 points among patients whose [ESS] score was at least 10 at baseline, compared with 3.1 points among those whose score was less than 10," he said.

Marital status was also examined as a covariate in the multiple regression model and appeared to have an effect. The mean PHQ-9 score decrease among the 475 married patients after CPAP was 4.0, compared with 3.0 among single patients and 2.3 among divorced patients, Dr. Bae said, noting that the difference between married and divorced patients was significant.

While the specific mechanisms contributing to the mood improvements associated with CPAP treatment in OSA patients can’t be ascertained from a retrospective study, the findings are fairly intuitive, according to Dr. Bae. When people sleep better, "a lot of things look better," he said.

Dr. Bae disclosed no relevant conflicts of interest.

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.