Goal 2: Reduce Human Disease

Understanding COPD Manifestations in Subjects without Overt Airflow Obstruction

What is the pathogenesis and appropriate treatment for subjects with chronic respiratory symptoms or imaging abnormalities who do not have overt airflow obstruction (and thus are not currently categorized as having COPD)?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

COPD is currently diagnosed by spirometry, but many other individuals (primarily smokers) have respiratory symptoms and/or imaging abnormalities that suggest lung damage. Identifying subjects with pre-obstruction manifestations of COPD could lead to more effective treatment and prevention.

Feasibility and challenges of addressing this CQ or CC :

COPD subjects often develop ongoing inflammation that persists long after smoking cessation. It is unknown when this cycle of inflammation begins or what causes it.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and the COPDGene Executive Committee

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32 net votes
47 up votes
15 down votes
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Goal 3: Advance Translational Research

Early prediction of cardiovascular disease by primary-care assessment

Tools for early assessment of cardiovascular disease have become available but not adopted in primary-care settings. Increased arterial stiffness is a well-known marker for advanced cardiovascular disease (CVD) and has been shown to be an independent predictor of cardiovascular mortality. In addition, arterial pulse wave velocity (PWV) has been readily accepted as a measure of arterial stiffness. Despite significant ...more »

Submitted by (@roy.wallen)

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

Details on the impact of addressing this CQ or CC :

In the US, 84 million adults will see their primary care physician for treatment of cardiovascular disease (CVD). CVD is responsible for an average of one death every 40 seconds. The direct and indirect costs of cardiovascular disease and stroke are approximately $315 billion, including the cost of health care services, medications to treat high blood pressure, and missed days of work. The World Health Organization states that 80% of premature heart disease and stroke is preventable. Focusing on assessing risk factors for cardiovascular disease, screening for individuals at risk, and then providing effective and affordable treatment to those who require it can prevent disability and death and improve quality of life.

 

In Europe, the European Society of Cardiology (ESC) has issued guidelines based on the weight of evidence in favor of the usefulness of screening for CVD by assessing arterial stiffness. These guidelines are supported by nonrandomized trials and suggest the development of randomized trials or meta-analyses. However, no guidelines exist in the US for screening for arterial stiffness from such organizations as the American Heart Association (AHA) and the American College of Cardiology (ACC). Existing guidelines to include assessment of cholesterol, lifestyle, obesity, and factors for risk are important. However, a simple, low-cost, objective measurement could be implemented at the point of primary care to improve early detection and treatment of CVD.

Feasibility and challenges of addressing this CQ or CC :

Screening capabilities and some level of clinical evidence exist for early detection of CVD. Therefore, implementation of a practice guideline in the US is very feasible. Studies and assessment from existing data such as have been completed by ESC can be replicated in the US and promulgated by AHA and ACC. This effort will require support from public and private entities, including universities, in order to see practice standards implemented.

 

Challenges to date include funding and the application of clinical protocols to support randomized studies or meta-analyses that will provide evidence for benefits of early screening. Further, public policy and current funding are focused on treatment rather than prevention. Existing reimbursement established by the Centers for Medicare & Medicaid Services (CMS) is focused on treatment rather than prevention and private insurance carriers have followed this same policy. Broader clinical study will support both the adoption of screening tools in primary care and broader reimbursement policy.

Name of idea submitter and other team members who worked on this idea : Roy Wallen

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5 net votes
8 up votes
3 down votes
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Goal 3: Advance Translational Research

Develop an Effective and Functional Biological Pacemaker

There is a need to develop a biological pacemaker for pediatric patients that would react to neurohumoral factors that normally modulate heart function, as well as adapt to the growing heart.

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Reduce risks associated with the increasing use implantable pacemakers. Increase reliability of artificial electrical pacemakers.

Feasibility and challenges of addressing this CQ or CC :

Animal studies have already demonstrated feasibility of cell- and gene-based as well as hybrid approaches.

The introduction of implantable medical devices using electrical impulses through electrodes placed in the heart to regulate its beating in patients whose native cardiac pacemakers fail— i.e., implantable electronic pacemakers— have permitted hundreds of thousands of individuals to live extended, relatively normal lives. Many advances since the introduction of implantable pacemakers into medical practice during the latter half of the 20th century have improved reliability, but their use still carries significant risks; e.g., lead fracture, infection, malfunction, and the need for replacement.

To date experimental cell therapy, gene therapy, and hybrid approaches have been used to create biological pacemakers in animal models. These incorporate the use of human embryonic stem cells or induced pluripotent stem cells or overexpression of the transcription factor, TBX18, to produce functional biological pacemakers in large animal models. Other gene therapy approaches have also been used to generate functional biological pacemakers in animals. These include overexpression of ion channels impacting diastolic membrane depolarization and excitability in non-pace making regions of large animal hearts. Beta-2 receptor or adenylyl cyclase overexpression represent other strategies that have been employed. Finally, a hybrid approach has used human mesenchymal stem cells loaded with the pacemaker gene HCN2is to induce pacemaker activity in large animals. Thus multiple approaches exist and collaboration is needed between investigative groups to overcome the challenge of creating and testing an effective and reliable biological pacemaker in humans.

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

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8 net votes
23 up votes
15 down votes
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Goal 1: Promote Human Health

What is the role of the environment in HLB disease etiology

It is clear that genetic sequence variation does not account for a substantial portion of disease burden. It is likely that the broad environment contributes to HLB disease via epigenomic alterations and interaction with genetic variants. There is an urgent need to understand the environmental contribution to disease as most exposures are modifiable and are targets for prevention interventions.

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Environmental exposures are clear involved in the pathogenesis of asthma, copd, CVD, and stroke. Understanding the environmental contribution may be critical for reducing disease burden for these common diseases.

Feasibility and challenges of addressing this CQ or CC :

Interventions to reduce disease burden are highly feasible in the next 5-10 years

Name of idea submitter and other team members who worked on this idea : Frank Gilliland

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4 net votes
11 up votes
7 down votes
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Goal 2: Reduce Human Disease

Prevent the Development of COPD

What can be done to prevent the development of COPD in individuals at increased risk. Quitting smoking before the development of COPD can prevent COPD development. What can be done to prevent COPD for individuals with other identified ris factors

Submitted by (@jsullivan)

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

Details on the impact of addressing this CQ or CC :

Several risk factors have been identified that identify individuals at risk for developing COPD including low birth weight, poor maximally attained lung function and the presence of asthma. Strategies to prevent COPD development in these individuals are needed.

Feasibility and challenges of addressing this CQ or CC :

The Lung Health Study demonstrated that smoking cessation prevents COPD progression. Studies of similar size and duration should be organized to address other risk factors.

Name of idea submitter and other team members who worked on this idea : COPD Foundation, COPDF MASAC

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15 net votes
18 up votes
3 down votes
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Goal 2: Reduce Human Disease

Should clinical primary prevention of ASCVD be guided by subclincal disease or estimated risk?

Current approaches to guiding use of clinical primary prevention interventions, e.g., statins and aspirin, are based on treating patients who exceed a specific risk threshold. The performance of risk estimation is good, but not outstanding, and results from clinical and population studies continue to support the value of new biomarkers. Given the widespread use of preventive therapies, the lack of untreated cohorts is ...more »

Submitted by (@david.goff)

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

Details on the impact of addressing this CQ or CC :

The size of the US and global population qualifying for treatment with a statin or aspirin for primary prevention of ASCVD is immense. Given the performance of risk estimation, even if risk estimation were universally implemented, patients would be misclassified with the consequence of being under or over treated. If treatment based on presence of subclinical disease is more cost-effective, the benefits of preventive therapies can be enjoyed by larger proportions of our population and more ASCVD can be averted. Given the ionizing radiation, albeit low intensity, associated with CT scanning, it is incumbent on the biomedical research community to document the advantages, if any, of a subclinical disease guided approach to provision of clinical primary prevention services for ASCVD.

Feasibility and challenges of addressing this CQ or CC :

Many people will be concordant for the two methods of guiding provision of therapy, about 65% of middle aged and older adults. That is, many people will be high risk and have subclinical disease and many people will below risk and not have subclinical disease. It is only the discordant people, i.e., high risk people without subclinical disease and low risk people with subclinical disease, who will be informative study participants. Hence, many people will need to be screened to identify the roughly 35% who are discordant, and would be treated differently by the two approaches.

 

People may be unwilling to accept randomization once they know the information about their estimated risk and presence or absence of subclinical disease. If a low participation rate among eligible persons is observed, an even larger population of screenees would be needed.

 

A vanguard phase could provide information about these potential challenges.

Name of idea submitter and other team members who worked on this idea : David Goff, Donald Lloyd-Jones, Phil Greeland.....

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-3 net votes
6 up votes
9 down votes
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Goal 1: Promote Human Health

Studying Health in Addition to Disease

Why do some people stop smoking after a stroke or myocardial infarction, whereas others do not? What motivates people who adopt a healthier diet and exercise program during their lifetime or after a significant health event? How can we promote healthier lifestyle choices at all stages of life? How do we ensure equitable health promoting activities for minorities, vulnerable populations, and lower socio-economic status ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Answering this critical question would enable us to have a more complete picture both of disease and of health.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to address this critical question because we need to expand our understanding of how people remain healthy or regain health, especially given the unhappy statistics concerning obesity, physical activity, blood pressure, diabetes, etc.

Few would disagree with the importance of studying the epidemiology, mechanisms, and progression of disease: research is focused on preventing or curing diseases. In addition to this disease-focused model, there are untapped opportunities to examine health and wellness. Borrowing from the field of Positive Psychology, which is the study of the aspects or characteristics of mental health (e.g., the strengths, values, behavior that contribute to well-being), we can expand this idea to study the aspects of those who remain healthy, who have retained health after disease, or who have successfully made healthy lifestyle changes. In terms of obesity, an example of this idea is Rena Wing’s National Weight Control Registry, which studies individuals who have successfully maintained long-term weight loss.

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

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135 net votes
176 up votes
41 down votes
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Goal 2: Reduce Human Disease

Cardiovascular risk and adverse event prediction & estimating net benefit in statin-treated individuals

Compelling Question: There is insufficient data to personalize the use of nonstatin or other preventive therapies in statin-treated patients. Equations could then be developed to predict CVD risk and to predict the risk of adverse events in statin-treated patients to guide intensification of therapy.

Submitted by (@jennifergrobinson)

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

Details on the impact of addressing this CQ or CC :

The 2013 ACC/AHA cholesterol guideline recommends statin therapy for the prevention of CVD events in moderate-high risk individuals. Many patients are still at increased CVD risk on statin therapy.

 

The potential for net benefit from CVD risk reduction therapies added to statin therapy depends on the absolute CVD risk in the statin-treated patient, the relative reduction in CVD risk from the added therapy, and the potential for net benefit.

Feasibility and challenges of addressing this CQ or CC :

This could be a pooling project of existing data from observational databases and clinical trials. Sophisticated pharmacoepidemiologic methods would be needed (and likely need to be developed) to draw appropriate inferences for application to clinical practice.

Name of idea submitter and other team members who worked on this idea : Jennifer Robinson MD MPH

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3 net votes
11 up votes
8 down 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 »

Submitted by (@bmdixon)

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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6 net votes
44 up votes
38 down votes
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Goal 2: Reduce Human Disease

Optimizing Cardiovasular (CV) Prevention Medicine Use

Heart attacks and strokes cause substantial morbidity and mortality, while implementation of cholesterol and other CV prevention guidelines remain low. Proposed NCQA on-statin in the last year among those with DM was 46% in national field testing, and about 75% in Kaiser Permanente (KP). KP has had some success overcoming barriers to statin, aspirin, and blood pressure medicine adherence. If the nation as a whole is ...more »

Submitted by (@ronald.d.scott)

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

Details on the impact of addressing this CQ or CC :

Improving treatment rates to CV guidleines improves the population health and can be cost saving to the system. Currently statin use among DM and in those with ASCVD Risk >= 7.5% is about 40%. If treatment improved to 60 or 80% many CV avents would be averted and downstream cost savings.

Feasibility and challenges of addressing this CQ or CC :

KP has achieved blood pressure control rates of about 90% demonstrating possibility of high control / treatment rates. Improving treatment rates where there is a treatment gap in cost saving CV prevention should be a priority.

Name of idea submitter and other team members who worked on this idea : Ronald D Scott, MD. Kaiser Permanente Integrated Cardiovascular Health Team

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-11 net votes
3 up votes
14 down votes
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Goal 2: Reduce Human Disease

Primary prevention statin trial in indivduals >75 years of age

Compelling question: There is insufficient randomized trial evidence for statins for primary prevention after age 75 years, as summarized in the recent 2013 ACC/AHA cholesterol guideline. T

Submitted by (@jennifergrobinson)

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

Details on the impact of addressing this CQ or CC :

The paradigm of "net benefit" introduced in this guideline cannot be applied in the absence of evidence that statins reduce ASCVD events and the adverse event rate of statins in this age group. There are likely significant differences in net benefit in subgroups of older adults as well due to competing causes of morality, comorbidities, and increase potential adverse effects on muscle function and quality of life.

Feasibility and challenges of addressing this CQ or CC :

This can be addressed in pragmatic trial design, but must include individual level randomization and placebo control to accurately assess treatment effects

Name of idea submitter and other team members who worked on this idea : Jennifer Robinson MD MPH

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-4 net votes
11 up votes
15 down votes
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Goal 1: Promote Human Health

THE RELEVANCE OF PREVENTION TRIALS

Prevention trials, implemented to reduce or delay progression to overt disease in a population at risk to the disease, are an important approach to health promotion. Therapies shown to reduce disease severity in patients with a specific disease are obvious, but not the only, candidates for a prevention trial in populations at high risk for prevalent diseases (such as heart failure, diabetes, COPD, asthma in children). ...more »

Submitted by (@media0)

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 impact of implementing such trials is considerable. They will clearly address an important component of NHLBI’s mission with respect to effectiveness of therapies and behavioral interventions, and it has minimal and clearly definable overlap with commercial trials of specific therapeutic products. It will also provide an important public health focus – preventing disease or reducing the impact of disease processes, thus potentially reducing chronic care costs and increasing years of useful life.

Feasibility and challenges of addressing this CQ or CC :

The biggest challenge in designing and implementing prevention trials is identifying the target, “at risk” population most likely to develop the clinical disease from known biomarkers or early signs/symptoms. Increasing availability of large, population-based registries or databases maintained for other purposes provides a very cost-efficient mechanism to electronically screen and identify “at risk” individuals. The same mechanism may also facilitate implementation of pragmatic, electronically managed, cost efficient trials.

Name of idea submitter and other team members who worked on this idea : Sonja McKinlay other Team Members: Susan Assmann and Paul Stark

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7 net votes
10 up votes
3 down votes
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