NATIONAL CENTER ON SLEEP DISORDERS RESEARCH
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Sleep Disorders Research Advisory Board Meeting Minutes
December 11, 2002

The 17th meeting of the Sleep Disorders Research Advisory Board (SDRAB) was convened at 8:45 a.m. on Wednesday, December 11, 2002, in the Natcher Conference Center on the campus of the National Institutes of Health (NIH) in Bethesda, Maryland. The meeting was adjourned at 3:30 p.m. Stuart Quan, MD, presided as Chair

TABLE OF CONTENTS

Attendees
Opening Comments
Adoption of June, 2002 Advisory Board Meeting Minutes
Introduction of New Members
Report of the Director NCSDR
National Children's Study: Dr. Tamar Lasky, National Institute of Child Health and Human Development
Workshop Report - Cardiovascular Consequences of Sleep-Disordered Breathing: Dr. Stuart Quan
Education Subcommittee
2003 Revised National Sleep Disorders Research Plan
New Agenda Item
Public Reports
Adjournment
Certification

NCSDR Home Page

Sleep Disorders Research Advisory Board Page

BOARD MEMBERS PRESENT

Dr. Stuart F. Quan (Chair)
Dr. Mary Carskadon
Dr. Kathryn Lee
Ms. Sandra McGinnis
Dr. Rafael Pelayo
Dr. Susan Redline
Dr. Michael Sateia

EX OFFICIO MEMBERS PRESENT

Dr. Carl E. Hunt, SDRAB Executive Secretary
Dr. Timothy Hays (for Dr. Israel Lederhendler)
Dr. Paul Nichols

LIAISON MEMBERS PRESENT

Dr. Deborah Ader
Dr. Harold Gordon
Dr. Nancy Pearson
Dr. Christopher Platt
Dr. Thomas Raslear
Dr. Roger Rosa
Dr. George Ruby
Dr. Ellen Witt

FEDERAL EMPLOYEES PRESENT

Ms. Pamela Anikeeff, NHTSA
Mr. Al Golden, NHLBI
Ms. Sue Rogus, NHLBI
Ms. Susan Sagusti, NHLBI
Ms. Ellen Sommer, NHLBI
Dr. Michael Twery, NHLBI

INVITED GUESTS PRESENT

Dr. Tamar Lasky, NICHD
Dr. David White (present by phone)

MEMBERS OF THE PUBLIC PRESENT

Robert Balkan, Restless Legs Syndrome Foundation
Jerome Barrett, American Academy of Sleep Medicine
Pat Britz, National Sleep Foundation
Darrel Drobnich, National Sleep Foundation
Christin Engelhart, American Sleep Apnea Association
Richard Gelula, National Sleep Foundation
Carey Pulvino, American Academy of Sleep Medicine
Judy Yore, Sleep Research Society

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I. OPENING COMMENTS - Dr. Stuart Quan

Dr. Stuart Quan, Sleep Disorders Research Advisory Board (SDRAB) Chair, welcomed the Board members, members of the public, and others in attendance. Dr. Quan noted that an important focus of the meeting would be review of and vote on the revised National Sleep Disorders Research Plan. Dr. Carl Hunt called attention to the materials in the meeting book, and he asked members to review the statement on confidentiality/ethics issues.

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II. ADOPTION OF MINUTES FROM JUNE 26, 2002, MEETING - Dr. Stuart Quan

Approval of the minutes of the June 26, 20002 SDRAB meeting was moved, seconded, and approved unanimously without further discussion.

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III. INTRODUCTION OF NEW MEMBERS

Dr. Hunt announced that two members will be leaving the Trans NIH Sleep Research Coordinating Committee (SRCC). Dr. Paul Nichols, NINDS, will be replaced by Dr. Merrill Mitler, and Dr. Karin Helmers, NINR, will be replaced by Dr. Mary Leveck.

Dr. Hunt also introduced the four new members appointed to the SDRAB effective July 1, 2002:

- Dr. Kathryn Lee, a Professor of Family Health Care Nursing at the University of California School of Nursing, whose specialty is sleep disruption and disorders in women

- Dr. Rafael Pelayo, an Assistant Professor in the Department of Psychiatry and Behavioral Science from Stanford University, a Sleep Medicine physician who has a special interest in educating health care workers and the general public about sleep, as well as pediatric sleep disorders.

- Dr. Susan Redline, Chief of the Division of Clinical Epidemiology at Rainbow Babies and Children's Hospital, Department of Pediatrics, Case Western Reserve University, who is a Sleep Medicine physician with a research focus on the genetic epidemiology of sleep disordered breathing

- Dr. Michael J. Sateia, Professor of Psychiatry and Director, Section of Sleep Medicine at Dartmouth-Hitchcock Medical Center, whose research interests include insomnia and its pharmacotherapy, alertness monitoring, and sleep curriculum development.

Dr. Hunt also announced two new Liaison Members of the SDRAB:

- Dr. Christopher Platt, Neuroscience Program Director, National Science Foundation

- Dr. George Ruby, Acting Director of Occupational Medicine, Occupational Safety and Health Administration, U.S. Department of Labor.

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IV. REPORT OF THE DIRECTOR, NCSDR – Dr. Carl E. Hunt

Dr. Hunt updated members on the National Center for Sleep Disorders Research (NCSDR) web site, www.nhlbi.nih.gov/sleep. He also introduced a new member of the NCSDR administrative staff, Ms. Pamela Palmer.

Dr. Hunt reported that NIH Sleep Research Funding has doubled from 1995 ($72,815,000) to 2001 ($145,085,000). There is, however, still substantial opportunity for growth.

Dr. Hunt discussed a new NHLBI/NIA RFA on the role of sleep disordered breathing (SDB) in metabolic syndrome, whose goal is to elucidate the relationships between SDB and obesity, hypertension, dyslipidemia, insulin resistance, and vascular inflammation. Applications are due by February 11, 2003. Other RFAs potentially related to sleep research were available in the Board briefing book, including a request for information on developing and applying nanoscience and nanotechnology to heart, lung, blood, and sleep disorders (due January 24, 2003).

Dr. Hunt responded to a previous request by Board members to provide reports from recent workshops on sleep issues (available in the Board briefing book). These included "The CVD Consequences of Sleep Disordered Breathing (draft);" "RLS: Diagnosis and Diagnostic and Epidemiologic Tools;" "Neurobiology of Sleep and Waking: Implications for Insomnia" (the report for which is on the NCSDR web site); "Sleep, Fatigue and Medical Training: Optimizing Learning and the Patient Care Environment" (which will be published in Sleep, March, 2003); and "Cardiovascular and Sleep Related Consequences of TMJ Disorders" (the report for which is on the NCSDR web site). Future meetings of potential interest to the Board (available in the Board briefing book) include the NCSDR-sponsored "Effects of Sleep Disorders and Sleep Restriction on Adherence to CVD Treatment Recommendations" (March 12-13, 2003).

Dr. Hunt reported on several other activities sponsored by NCSDR. A monograph on sleep and sleep disorders in women will be published in 2003 in an American College of Obstetrics and Gynecology monograph. The NCSDR bookmark is being revised to include up-to-date information about NCSDR programs and contact resources.

Dr. Hunt concluded by reviewing the process leading to the final draft of the 2003 Revised National Sleep Disorders Research Plan (see VIII below). This included creating a 14-member research task force, developing a draft, active participation by the Trans-NIH Sleep Research Coordinating Committee, and obtaining public comments at national sleep research meetings and from posting the draft plan on the NCSDR web site for 2 months.

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V. NATIONAL CHILDREN'S STUDY - Dr. Tamar Lasky, National Institute of Child Health and Human Development (NICHD)

Dr. Tamar Lasky presented the National Children's Study (NCS), a 21-year prospective cohort longitudinal study of 100,000 people whose goal is to determine the basic mechanisms, interrelationships, and effects of chemical, physical, behavioral, and socio-cultural environmental factors on child health and development. This national study is sponsored by NICHD, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, and the Environmental Protection Agency. The study is designed to identify safe/dangerous exposure levels and attribute causality for child health risks. NCS study subjects will include children and their families, possibly beginning with enrollment of women prior to or at least during pregnancy.

Priority areas of focus of the NCS will include the impact of environmental exposures on birth defects, fetal growth, neurobehavioral and neurocognitive development, physical growth, injury, asthma, and obesity. Key measures anticipated are environmental samples, biomarkers for chemical exposures, and personal interviews/histories.

NCS will have multiple enrollment sites across the U.S. The planning process includes large-scale collaboration mediated by an interagency coordinating committee, a federal advisory committee and 22 working groups, each comprised of 10-20 federal and non-federal scientists. The initial authorization for the project was $18 million, with additional funding to be appropriated over time. NCS planners are currently developing methodologies and pilot studies for the initiative, with enrollment scheduled to begin in 2005. The study web site, http://NationalChildrensStudy.gov, is already posting useful information, such as a database of biomarkers for chemical exposures and outcomes.

Dr. Carl Hunt and Dr. Mary Carskadon are members of the Development & Behavior Working Group and have developed a 2-page draft of a core hypothesis for the NCS related sleep problems and disorders in children. It is important to that information on sleep be collected because sleep affects so many study variables, such as injury, development, and metabolic outcomes.

Several Board members expressed the opinion that sleep should be a core priority, since more children are likely to have sleep deprivation than other environmental risks, such as lead exposure. Members suggested a variety of ways that sleep could be included in the study as it interrelates with other priorities as an exposure or an outcome, such as:

-Sleep disorders as an early indicator, correlate, or outcome of attention deficit hyperactivity disorder (ADHD).
-SDB and asthma in childhood.
-Prematurity and the increased the risk of childhood sleep apnea.
-The effects of various childhood exposures on development of sleep apnea.
-Cultural issues, such as the impact of co-sleeping.
-Sleep problems in under-served, under-represented populations.
-Ethnic minorities and sleep apnea.

In addition, Board members noted that just asking how much sleep a participant gets during the interview would provide critical information. Discussion also included the need to develop easy, inexpensive, and reliable tools to measure sleep disturbances in children. The next step will be to develop a core content of sleep-related information that will need to be collected in all enrollees at to-be-determined intervals. Advisory Board members are encouraged to provide input to Drs. Carskadon and Hunt to assist in developing the sleep-related core content for the study design.

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VI. WORKSHOP REPORT: Cardiovascular Consequences of Sleep-Disordered Breathing - Dr. Stuart Quan

Sleep Disorders Research Advisory Board Chair Dr. Stuart Quan reported on the September 2002 workshop sponsored by NCSDR and NHLBI related to the CVD consequences of SDB. Key points include the following.

- SDB increases the risk of hypertension; the higher a patient's score on the apnea-hypopnea index by quartile, the higher the risk. Possible mechanisms are increased sympathetic activation and endothelial dysfunction. Increased levels of endothelin, a vasoconstrictor peptide, have been found in patients with SDB. Some studies have also found diminished endothelial cell production of nitric oxide, a vasodilator. Intermittent hypoxia and sleep deprivation may each promote production of pro-inflammatory cytokines that impair endothelial function.

- SDB is associated with an increased prevalence of cardiovascular disease (CVD) (including hypertension, myocardial infarction, stroke, and congestive heart failure). The risk factors for SDB and CVD are highly interrelated. For example, obesity is a major risk factor for SDB, hypertension, and CVD. Sleep deprivation caused by SDB appears to contribute to the development of insulin resistance and may be a risk factor for obesity. Obesity and SDB may interact to produce CVD, possibly through the secretion of adipokines. Inflammation also appears to play a role in the pathogenesis of CVD. Emerging evidence suggests that the intermittent hypoxia caused by SDB may trigger an inflammatory response and the release of substances implicated in coronary heart disease.

- Important future research priorities include 1) prospective epidemiological studies to elaborate the relationship among inflammatory biomarkers and hypertension and SDB; and 2) studies to understand the role and mechanisms of the sympathetic nervous system, to disentangle the complex interactions of SDB and diverse CVD risk factors, to identify subpopulations at special risk, and to develop non-invasive biomarkers of vascular disease that could be useful both for diagnostic and for treatment studies in order to assess the role of SDB as a risk factor for CVD and the impact of therapy..

- SDB has been associated with hypercoagulability, and patients with pulmonary embolism or deep vein thrombosis have a higher incidence of SDB. While some studies have observed enhanced platelet adhesion and aggregation with SDB, larger, well-controlled studies of SDB and hemostasis are needed to define the relationship and mechanisms of action and, ultimately, determine whether patients with SDB should be treated for hypercoagulability.

- SDB is common in patients with heart failure. Epidemiological research is needed on the prevalence of SDB in those with asymptomatic heart disease, as well as additional studies on the impact of SDB on heart failure and the impact of treating sleep apnea on cardiac function. - While cardiac arrhythmias are seen in some patients with SDB, better studies are needed regarding incidence and prevalence and to determine: 1) whether an independent association exists between arrhythmias and SDB or if they are simply a sign of underlying heart disease; and 2) whether arrhythmias occurring during SDB have prognostic value.

- Additional study of gene-environment interactions is needed to better characterize the obstructive sleep apnea (OSA)/SDB/CVD phenotype. An important step would be to include SDB assessment in CVD epidemiological studies. Research is also needed to identify genes common to SDB and CVD and to determine whether SDB patients with different genetic backgrounds have differing susceptibility to CVD.

The workshop participants concluded that basic research and animal studies of underlying mechanisms were needed to answer the critical research questions. To carry out the epidemiologic research suggested, it will first be necessary to develop simpler screening tools than today's polysomnograms. Participants also agreed that major clinical intervention trials were not warranted until SDB phenotypes, causal mechanisms, and effective, well-tolerated therapies became available.

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VII. EDUCATION SUBCOMMITTEE - Ms. Sue Rogus, Ms. Ellen Sommer

The Sleep Well. Do Well. Star Sleeper Campaign

Ms. Ellen Sommer updated the Board on the Sleep Well. Do Well. Star Sleeper campaign, which features Garfield as its "spokescat." Targeting children ages 7-11 as well as parents, teachers and principals, pediatricians, and school nurses, the campaign promotes at least nine hours of sleep a night for children to do their best in all endeavors.

In 2002, promotions included an audio news release suggesting getting nine hours of sleep a night as a New Year's resolution for children, a media event with third graders in San Antonio, another media event in connection with the American Academy of Pediatrics meeting in Boston, and a second "back to school" campaign.

In addition, 1,100 second and third graders participated in the "How I Get a Heap of Sleep" contest, sending in three ways they get a good night's sleep. The contest included tested classroom activities that reached one million children.

The campaign's web site http://www.nhlbi.nih.gov/health/public/sleep/starslp/ also continues to evolve, now featuring interactive games with sleep messages, such as a create your own Garfield comic and "Mission Z" in which children work to turn off alien sound waves that disturb sleep. Millions of visits to the site have been recorded, and thousands of links to the site appear on search engines and related web pages. A separate portal for teachers contains activities and lesson plans, and portals also exist for parents and pediatricians with relevant information and tips.

Board members raised the possibility of having the site (or a related CD) available in pediatricians' offices and asked whether any outcome evaluation has been developed yet. Ms. Sommer explained that media exposure and other process evaluation data were easy to obtain. However, an outcome evaluation that would survey users regarding knowledge or behaviors was complicated by the need for Office of Management and Budget clearance and would be expensive. The group discussed using an RFA to conduct evaluation and getting the sleep community to help. In response to questions, Ms. Sommer noted that the site does not contain links to medical help for sleep disorders, although it does link to the NCSDR site. She also reported that testing has shown that children are very familiar with Garfield, view him positively, and believe him, and that he also has strong appeal for adults.

Ms. Rogus reported that the American Academy of Pediatrics, the National Association of School Principals, the National Association of School Nurses, and various elementary schools are important partners in the Garfield campaign. The Duluth, Michigan, public schools served as a prototype and tested the campaign materials. All schools can download the materials from the campaign web site. Other Educational Activities

The high school curriculum on the biology of sleep, sleep disorders, and biological rhythms, discussed at the June, 2002, Board meeting, will soon appear on the NHLBI and NIH Office of Scientific Education's web sites. The curriculum is also being presented at the 2003 meeting of the National Science Teacher's Association.

A sub-panel of the Working Group on Sleepiness and Adolescents (ages 13-22) presented a two-hour session at the annual meeting of the American Academy of Pediatrics. The Group is also developing two papers for submission to the Pediatrics on the state of the science and on clinical approaches to sleepy adolescents.

Future educational activities will include enhanced promotion of the Garfield campaign, revising the narcolepsy fact sheet, and disseminating the high school curriculum and Working Group papers.

Ms. Rogus also noted that partner groups helped with educational activities beyond the Garfield campaign, including examples such as Jordan's Furniture Stores, which handed out sleep materials with children's bedding; Sweet Dreamzzz in Detroit, a group of volunteer mothers; and the Better Sleep Council, which has been working with the bedding industry. Board members suggested that sleep advocates, family physicians, and nurse practitioners might also be appropriate educational partners.

Dr. Quan asked Ms. Rogus to report back to the Board on the issue of snoring toys, which Dr. Pelayo described as sending the incorrect message that snoring is funny, rather than a potential health concern. Dr. Pelayo will contribute background information.

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VIII. 2003 REVISED NATIONAL SLEEP DISORDERS RESEARCH PLAN - Dr. David White, Dr. Stuart Quan, and Board Members

Dr. David White, Chair of the Task Force that developed the 2003 Revised Sleep Research Plan, provided an overview of the Plan, which features 30 scientific sections with background information, progress since the 1996 Research Plan, and future research recommendations. He reviewed the research recommendations highlighted in the Executive Summary, including the following:

1. An improved understanding of all aspects of the neurobiology and functions of sleep;

2. Enhanced understanding of the impact of reduced or restricted sleep on both behavior and neurobiologic and physiologic functions across the entire age spectrum;

3. Improved understanding of the processes that lead to specific sleep disorders-the most important of these are insomnia, restless legs syndrome, sleep apnea and disorders of ventilatory control, and primary disorders of hypersomnolence;

4. Careful assessment of the normal human sleep phenotypes and the normal range of variation;

5. Development of new treatments for sleep disorders, with comprehensive outcome evaluation and appropriately-powered clinical trials leading to clinical management guidelines for the following disorders, which represent the greatest needs and opportunities: adult and pediatric obstructive sleep apnea, insomnia, narcolepsy and restless legs syndrome;

6. How sleep affects, and is affected by, a variety of disease processes, including medical conditions, neurologic disorders, psychiatric, alcohol and substance abuse, and pediatric genetic and neurodevelopmental disorders;

7. Development of sleep educational programs for health professionals and the public;

8. Greater application of new technologies and methodologies to sleep research and patient management;

9. Expanding research training, which is essential to expanding sleep research.

Plan Approved, with Revisions

The Task Force was complimented by the Advisory Board for creating a balanced, logically flowing document responsive to the needs of the sleep community. The Board unanimously approved the Research Plan with the understanding that the minor modifications recommended by the Board will be made by the NCSDR.

Implementation of Revised Research Plan

Following final editing by NCSDR staff, the Research Plan will go to Dr. Lenfant, Director of NHLBI, and Dr. Zerhouni, Director of NIH, for their review and approval. The final document will be posted on the NCSDR web site, with printed copies available thereafter. Discussions are in process regarding possible publication of the Executive Summary in the journal Sleep and perhaps other scientific journals.

The Advisory Board discussed recommendations for implementing the Plan. Suggestions included:

1. Selecting one or two topics and bringing in experts to future meetings to advise the Board on implementation strategies;

2. Relying on the Board's own expertise to making recommendations; or

3. A combination of the above. Members expressed concerns about making decisions too quickly or focusing too narrowly, especially in light of the opportunities for cross-disciplinary activities.

To take the first step in implementation of the Plan, the Advisory Board addressed the need to develop novel tools for assessing sleep and measuring sleep-related exposures and outcomes methods and for assessing sleepiness in large studies. Sensitive, specific, and reliable tools are needed to determine the function of sleep and to measure the physiologic processes leading to sleep deprivation.

The Board also made the following suggestions for other priority topics for implementation:

- Relationship of learning, memory, and sleep.
- Sleep and the development of neurocognitive function from childhood through adulthood.

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IX. NEW AGENDA ITEM: WHERE ARE SLEEP GRANTS REVIEWED?

Dr. Quan reported that Dr. Allan Pack has requested that the Advisory Board collect information on where NIH sleep research applications are reviewed, and how this process might be altered by further reorganization of study sections. For example, Dr. Pack said that the pulmonary section does not currently review proposals related to SDB. Dr. Hunt agreed to investigate this issue and report back to Dr. Quan and the Board.

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X. PUBLIC REPORTS AND OTHER COMMENTS

Several organization representatives reported on recent activities. Written reports submitted were available to Board members in their meeting materials

Mr. Jerome Barrett from the American Academy of Sleep Medicine advised the Board that the Academy has relocated to Chicago. Many staff are new, including Carey Pulvino, who handles the Sleep Medicine Education and Research Foundation, and Judith Yore, who will work with the Sleep Research Society (SRS). Recent Academy activities include working on Sleep Medicine certification by the American Board of Medical Specialties and development of an ACGME approved fellowship program in Sleep Medicine.

Mr. Bob Balkan from the Restless Legs Syndrome Foundation updated the Board on a May workshop held at NIH on RLS diagnostic and epidemiologic tools. In addition, the Foundation launched a database of health care providers with expertise in RLS on its web site and recently held its first national RLS patient meeting.

Ms. Christin Engelhardt, Executive Director of the American Sleep Apnea Association, reported on public education activities including the involvement of actor George Kennedy as a spokesperson. The Association also is working with the American Society of Anesthesiologists on pre- and post-surgery guidelines for sleep apnea.

Mr. Richard Gelula, Executive Director of the National Sleep Foundation (NSF), reported on the recent national summit on drowsy driving, and on new pediatric sleep guidelines. In March, 2003, NSF and the National Institute on Aging will sponsor a Congress on Sleep, Health and Aging. NCSDR is also a co-sponsor for this conference. Aging will an important focus for National Sleep Awareness Week (March 31-April 6, 2003).

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XI. ADJOURNMENT

Dr. Quan thanked the participants and adjourned the meeting at 3:15 PM.

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XII. CERTIFICATION

We certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.

Stuart Quan M.D., Chair
Sleep Disorders Research Advisory Board

Carl E. Hunt, M.D., Executive Secretary
Sleep Disorders Research Advisory Board

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