Showing 8 ideas for tag "obstructive"

Goal 2: Reduce Human Disease

Can Psychological Science Improve Weight Loss?

Will sensitivity to the psychological aspects of obesity, including lifestyle priorities and motivations, improve the efficacy of long-term effectiveness of weight loss and obesity prevention interventions?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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A primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Feasibility and challenges of addressing this CQ or CC

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.
In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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74 up votes
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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 »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

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 2: Reduce Human Disease

HEALTH CARE DISPARITIES IN DIAGNOSIS AND TREATMENT OF COMMON SLEEP AND CIRCADIAN DISORDERS

There is evidence of a higher prevalence of sleep and circadian disorders in different ethnic groups. This is true for both adult and pediatric subjects. There is also evidence that minority populations in lower socioeconomic groups do not seek evaluation for sleep disorders as frequently as other segments of our population. There is also evidence that they are less adherent to treatments such as nasal CPAP for obstructive... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Sleep disorders are more common in minority populations. Moreover, these populations have higher rates of the known consequences of these disorders such as stroke, myocardial infarction, hypertension, resistant hypertension. Despite this, current population studies such as the Sleep Heart Health Study have included only a very small percentage of African Americans. The impact of this would be the following:

a. Elucidating the basis of barriers to case identification in these group
b. Designing specific intervention to overcome these barriers.
c. Developing methods to improve adherence to therapy in this group.
d. Removing sleep and circadian disorders as a risk factor for consequences such as stroke, cardiovascular disease and resistant hypertension in minority populations

Feasibility and challenges of addressing this CQ or CC

There is a developing interest in this area in the field of circadian and sleep research. There is a developing knowledge base about health disparities in sleep and circadian disorders. Minority institutions such as Morehouse have developing programs in this area. We also have mobile technology that facilitates study of sleep and circadian disorders in minority populations.

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

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163 up votes
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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 »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

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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156 net votes
211 up votes
55 down votes
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Goal 3: Advance Translational Research

DEVELOPMENT OF BIOMARKERS FOR SLEEP INSUFFICIENCY, CIRCADIAN DISRUPTION AND SLEEP DISORDERS trending idea

There is an urgent need to develop quantifiable biomarkers for acute sleep loss, chronic sleep insufficiency, circadian disruption and sleep disorders such as obstructive sleep apnea. These problems are highly prevalent but currently we do not have biomarkers to use for case identification, prognosis, or assessing response to therapy. There are currently small studies that indicate the feasibility. A recent workshop... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The following will be the impact of addressing this critical challenge:

  1. Having an assessment that can be used following a crash to assess the level of sleep loss of the driver.
  2. Having a method to assess chronic sleep insufficiency as a potential pathogenetic process in patients with cardiovascular disease, hypertension, etc.
  3. Having a method to estimate circadian phase so that in patients with chronic insomnia one can identify individuals with delayed sleep phase.
  4. Having a technique to establish magnitude of circadian disruption to assess its role in pathogenesis of diseases such as cardiovascular disease.
  5. Add a molecular biomarker to other techniques to screen for obstructive sleep apnea in high risk populations such as obese commercial drivers.
  6. Utilize a biomarker signature to identify who with obstructive sleep apnea will be particularly at risk for downstream consequences such as cardiovascular disease.
  7. Develop the equivalent of HbA1C to assess therapeutic response to CPAP
Feasibility and challenges of addressing this CQ or CC

The first challenge is to identify a signature for each of these use cases. This will require initial studies in a small number of well phenotyped subjects with all the “-omic” techniques. Thereafter, these multiple cohorts, already available with blood samples, etc. and relative phenotype can be used for validation purposes.

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

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240 up votes
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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 »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

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

How can we better understand regional tissue heterogeneity in lung disease?

Many lung diseases (IPF, COPD) are characterized by marked heterogeneity at the tissue level. Unfortunately, most of the tools we currently employ to understand lung disease are unable to elucidate the mechanisms that result in regional heterogeneity. Clinical studies and animal models, while invaluable, generally assume that all lung tissue is similarly affected based on the presence or absence of diagnostic criteria... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Emerging evidence suggests that diseases such as IPF and COPD have observable phenotypes at the cellular and tissue levels long before the disease is clinically apparent. Thus seemingly healthy patients may have some regions of the lung affected by the same pathophysiologic processes that drive clinically apparent disease. By changing the focus of investigation from the presence or absence of disease in a given patient to the presence of absence of disease in a given region, several advantages emerge: (1) pathophysiologic mechanisms may be investigated earlier in the natural history of a disease, when interventions are more likely to be of benefit; (2) early investigation favors the discovery of distinct disease subgroups that are masked in more severe disease; and (3) a single patient may provide multiple affected and unaffected disease regions, allowing him or her to serve as their own control. Recently, advances in next-generation sequencing have made it possible for the entire transcriptome of a single cell to be analyzed. It is reasonable to believe that in the next 10 years single cell epigenome, proteome, and metabolome profiling will become routine. However, it seems less obvious how these methodologies can be employed to better understand the drivers of regional differences in lung disease. While technically difficult, studies applying high-throughput technologies to the discovery of regional differences will be invaluable to our understanding of lung disease.

Feasibility and challenges of addressing this CQ or CC

To address this critical challenge, at least five technological hurdles will have to be addressed: (1) technologies such as laser capture microdissection which allow for the isolation or cells from specific areas of the lung will need to improve; (2) technologies allowing for culture of multiple cell types on a single artificial substrate (to allow for experimental manipulation of cellular “communities”) will need to emerge; (3) collaborative networks will need to emerge whereby datasets from multiple labs can be integrated; (4) bioinformatics and statistical methods capable of filtering massive “omics” data sets from multiple cell types will need to be refined; and (5) researchers with the skills necessary to distil large descriptive datasets into testable hypotheses will need to be trained. While these hurdles are great, they must be overcome in order to translate the promise of next-generation sequencing techniques into an improved understanding of the drivers of regional heterogeneity in lung disease.

Name of idea submitter and other team members who worked on this idea Bradley Richmond

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