Goal 2: Reduce Human Disease

Sleep Apnea

Does treatment of sleep apnea prevent cardiovascular disease?

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Goal 2: Reduce Human Disease

Clinical Trials in Pediatric Sleep Disorders

Effectiveness of medications for cataplexy in children.

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Pediatric sleep experts agree that there appears to be a mini-epidemic of narcolepsy in children currently, characterized by acute onset of disease with severe symptoms and difficult to control cataplexy, in very young children. No drugs are approved for treatment of cataplexy in children, and drugs typically used in adults are not FDA-approved for use in children. A multicenter trial would be needed in order to accumulate sufficient cases for a randomized controlled trial.

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Goal 2: Reduce Human Disease

Sleep Apnea

Does treating sleep apnea benefit patients with obstructive lung disease?

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Goal 2: Reduce Human Disease

What causes the structural abnormalities that cause sleep apnea, and how can they be prevented?

It is estimated that up to 28% of the population suffer from sleep apnea, which impairs functioning and reduces quality of life, while increasing risk of accidents and a variety of cardiovascular, metabolic, and neuropsychiatric diseases. A large portion of sleep apnea cases are caused by abnormal oro-nasal-maxillo-mandibular features that result in crowding of the upper airway, making it vulnerable to collapsing or ...more »

Submitted by (@bmdixon)

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Obstructive sleep apnea (OSA) is a common condition, which causes chronic fatigue and daytime sleepiness, as well as cognitive impairments affecting learning, concentration, and memory. Over the long term, it increases many health risks, including accidents, cardiovascular disease, and depression. OSA is characterized by partial, or complete, blockage of the airway during sleep, so that breathing repeatedly pauses or airflow is limited, causing repeated arousals from sleep. It is usually secondary to a narrow, or collapsible, airway due to either 1) obesity or overweight, or 2) abnormal morphology of the mandible or maxilla bones, which crowds facial structures, such as the tongue and nose, narrowing the pharynx. The causes of obesity are already being well studied, but there is relatively little research on the etiology of the structural abnormalities involved in OSA. Abnormalities of facial structure are widespread in the population causing, not only OSA, but also orthodontic problems that require many to get braces or have wisdom teeth extracted, and widespread temporomandibular joint (TMJ) problems. However, multiple studies have documented that these abnormalities are almost completely absent from populations living a preindustrial, agrarian or forager, lifestyle, making them a “disease of civilization”. In particular, the abnormalities are associated with consumption of a modern diet of processed foods during prenatal, infant, and early childhood development.

Feasibility and challenges of addressing this CQ or CC :

Current evidence implicates three factors in the development of these structural abnormalities: prenatal maternal nutrition (especially vitamin K2 status), breastfeeding vs. bottle-feeding, and frequency of consumption of tough foods after weaning (which provides exercise to the jaw). We need to form a large cohort and study orthodontic development prospectively from fetal development through mid-childhood, with data on diet, feeding practices, and physiological measures of nutrient status. Measurement methods are available using existing technologies to collect the necessary data on each of these measures. Determining the causes responsible for these structural abnormalities will enable further research to demonstrate effective methods of preventing them. Given that many patients with OSA are rendered so miserable by it that they undergo maxillomandibular advancement surgery to correct it, an expensive procedure with a lengthy recovery period, prevention would be a far better solution. This research will move us a big step closer to a future without sleep apnea and its formidable collection of negative effects on health and functioning.

Name of idea submitter and other team members who worked on this idea : Bonnie Dixon

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Goal 2: Reduce Human Disease

Can At-home sleep studies change the rural area diagnosis of obstructive sleep apnea

At home sleep tests or personal monitors (PM) have been shown to effectively provide an adequate diagnosis of OSA with the proper pre-screening tests and evaluation. These methods can be adopted by hospitals and if used effectively can save money to the patients and healthcare facility. With the Affordable Healthcare Act the focus is on providing quality care for less money, but many hospitals are slow to adapt. Sleep ...more »

Submitted by (@jeremyplambeck)

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Setting up a protocol for rural hospitals, or all healthcare facilities in developing and taking care of patients with sleep disorder breathing.

Name of idea submitter and other team members who worked on this idea : Jeremy Plambeck

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Goal 2: Reduce Human Disease

Sleep Apnea - Diagnostic Test

The notion that in order to be treated with CPAP for sleep apnea you first must have a diagnostic test, which involves either a sleep laboratory or a home study, needs to be examined.

Submitted by (@nhlbiforumadministrator)

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This idea is far reaching and possibly ahead of the curve a bit but it represents a direction that the sleep apnea field eventually should explore. Consider developing a clinical diagnosis of sleep apnea based on clinical symptoms and exam findings and then randomized those patients meeting the definition to a trial of autocpap for 3 months or to a traditional evaluation (home diagnostic test then APAP) for 3 months. Close follow up is necessary but with wireless telephony now available for CPAP and estimates of AHI available through CPAP adherence downloads, this study is feasible. If such a case diagnosis of sleep apnea can be developed (and I believe it can), then many more patients may be able to be treated. This approach, if successful, would shake-up the field considerably and potentially opens up treatment to many more OSA sufferers.

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Goal 2: Reduce Human Disease

What are the biological consequences of sleep loss or disruption and how can they best be avoided?

Arousals in obstructive sleep apena (OSA) are life saving, but the associated disruption of sleep is now thought to cause cognitive impairment, increased risk of high blood pressure and atherosclerosis, as well as glucose intolerance and metabolic syndrome. The mechanisms for these downstream effects, however, are not well understood. Can these specific pathophysiological mechanisms be identified, and can ways for mitigating ...more »

Submitted by (@csaper)

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By identifying the mechanisms by which sleep loss or disruption affects cognitive, cardiovascular, and metabolic function, we hope to find key regulatory points for which interventions may be developed. For example, if we can allow respiratory reflex responses to reopen the airway without EEG activation during OSA, we may be able to forestall some of the cognitive consequences of inadequate sleep. If we can prevent the autonomic responses associated with the EEG arousals and increases in respiratory drive, we may be able to block the repetiive elevations of blood pressure that lead to long term hypertension and accelerated atherosclerosis. If we can identify the reason for metabolic derangement associated with OSA, we may find, for example, that it is due to circadian misalignment and find ways to realign the sequence of metabolic events with the actual wake-sleep patterns of the patients. Finally, if we can potentiate the respiratory reflexes that re-establish the airway in OSA, without triggering the other components of arousals, we may be able to minimize or prevent the apneas. While current methods for treating OSA (e.g., CPAP and dental appliances) help many people, many others cannot tolerate these devices, and we require additional modes of therapy to mitigate the consequences of OSA.

Feasibility and challenges of addressing this CQ or CC :

The methods are currently available to address the questions that are raised above. The revolution in methods for evaluating the functions of neural circuits, using optogenetics and chemogenetics, for example, should allow us to identify brain circuits that are involved in the various components of the reflex responses to apnea. We can examine their neurotransmitters and receptors, and design new therapies based on manipulating CNS circuitry. Methods for assessing ongoing autonomic, respiratory, and metabolic responses in genetically mutated mouse modesl may require further miniaturization of various physiological methods, but this field is also rapidly advancing. Finally, methods for examining ongoing changes in neuronal activity in the living brain of awake mice are rapidly advancing.

Name of idea submitter and other team members who worked on this idea : Clifford B Saper, MD, PhD

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Goal 3: Advance Translational Research

The effectiveness of a protocol-based screening in treating common COPD comorbidities

Does a protocol-based screening for commonly occurring comorbid conditions in patients with COPD (eg. CAD, CHF, depression, sleep apnea) improve management and outcomes for patients with COPD?

Submitted by (@dmcgowan)

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Many times co- morbidities are not address appropriately in patients with COPD- a protocol- based screening would support better identification and adherence to guidelines and would improve management and outcomes of individuals with COPD>

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Goal 2: Reduce Human Disease

Sleep Apnea

The general area is that of preoperative risk management of sleep apnea patients undergoing major surgery. This field is burgeoning with clinical activity. A large amount of healthcare dollars are expended annually in order to detect sleep apnea and offer therapy that is of unproven value. Most all of the data is retrospective case series or a mixture of retrospective and prospective cohort studies. Yet, across the country, ...more »

Submitted by (@nhlbiforumadministrator)

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The existing data shows that sleep apnea may be moderate risk factor for poor outcomes and complications from surgery but the magnitude of the risk and the degree to which sleep apnea therapy modifies this risk is not known and won’t be determined without larger scale trials. This field desperately needs some randomized trials to answer some of these questions. Trials which randomize patients undergoing some major surgery to a sleep apnea treatment with CPAP if OSA is diagnosed before surgery  vs. treating with CPAP after surgery in the post operative period is one such study that could be performed.

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Goal 2: Reduce Human Disease

SLEEP DISORDERS AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE

There is developing evidence that sleep disorders, in particular obstructive sleep apnea and inadequate sleep, can influence the course of other chronic diseases. Observational studies show that CPAP treatment of patients with pre-diabetes who have OSA reduces the incidence of future diabetes. Moreover, animal and human data indicate that insufficient sleep and sleep apnea can affect the rate of progression of neurodegenerative ...more »

Submitted by (@jnoel0)

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This question will have considerable impact. Sleep apnea is an independent risk factor for insulin resistance. Moreover, observational studies show that treatment of OSA reduces the rate of future diabetes compared to that which occurs in untreated OSA. Therefore, identifying OSA and treating this could have a profound impact on reducing the rate of diabetes, i.e., a preventative strategy.

 

Both sleep loss and obstructive sleep apnea have also been shown to be risk factors for subsequent development of Alzheimer’s disease. This has been shown in mouse models and in epidemiological studies to address whether insufficient sleep and sleep apnea are independent risk factors for development of Alzheimer’s disease, in particular accelerating their onset. Determining whether this is so and whether interventions to treat these sleep disorders delay onset of diabetes and Alzheimer’s disease would have profound public health significance.

Feasibility and challenges of addressing this CQ or CC :

These disorders are extremely common so that recruitment of subjects is not challenging. Moreover, new technology reduces protocol burden to assess individuals. All studies can be done in the patients’ home. There are existing cohort studies focused on diabetes and the Alzheimer’s Center program that could be used for these studies. Thus, the studies are extremely feasible in the near term.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 2: Reduce Human Disease

UNDERSTANDING SLEEP AND CIRCADIAN DISORDERS AT A BASIC MECHANISTIC LEVEL

We need to understand sleep and circadian disorders at a more mechanistic level. This applies to both the pathogenesis of these disorders and to their impact on health. New neurobiological and molecular tools facilitate this research. The focus needs to be not only in brain but also the impact of these disorders on future of peripheral organs. The elucidation of the fundamental functions of sleep and the impact of ...more »

Submitted by (@jnoel0)

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Much of the research on the consequences of sleep/circadian disorders has focused on their consequences or behavior. This type of research needs to be continued and there are new opportunities in this area. These behavioral studies need to be established in model systems to parallel studies in humans. In addition, new neurobiological approaches, including optogenetics and use of DREAD, provide new tools for this investigation. Moreover, we now have powerful molecular tools to evaluate effects of sleep/circadian disorders both in humans and animal models. These include microarrays, RNA seq, etc. Moreover, genetic studies, e.g., in restless legs syndrome, have identified gene variants conferring risk for the disorder. We do not know, however, how these particular genes are involved in the pathogenesis of the disorder or whether they represent potentially targets for drug intervention. There is a need for studies both in animal models and in humans to elucidate the function of these genes. Studies in other areas are obtaining stem cells from biopsies in patients and then turning these into relevant target cells such as neurons to elucidate gene function using in vitro approaches.

The impact of this effort will be the following:

 

a. Taking our understanding of pathogenesis of sleep and circadian disorders to a new level.

b. Understanding the consequences of sleep and circadian disorders on different end organs at a more in-depth molecular level.

Feasibility and challenges of addressing this CQ or CC :

The sleep and circadian field have access to all the major cells systems for these studies—C. elegans, aplysia, Drosophila, zebra-fish, mice, etc. Moreover, there are already gene variants identified in human studies which require follow-up functional studies. The field has the expertise in all of the techniques described above. Moreover, there are more validated animal models for many of the common sleep disorders. Thus, this new approach is very feasible. 

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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