Goal 1: Promote Human Health

Lung Resilience

What is the dynamic range of homeostasis (limits of resilience) for lung biology? What makes a lung resilient across the life span and to environmental insults?

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

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

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7 up votes
8 down votes
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Goal 3: Advance Translational Research

Identification of autoantigens that elicit pathogenic immune responses in cardiovascular diseases

Pathogenic immune responses participate in the pathogenesis of many cardiovascular diseases. However, the autoantigens and foreign antigens that elicit the pathogenic immune responses have been poorly identified. Currently, the regulatory mechanisms on immune responses associated with diseases got some attentions. But, without detailed characterizations of this wide spectrum of autoantigens and foreign antigens in patients... more »

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

Feasibility and challenges of addressing this CQ or CC
  1. use peptide/protein based microarray to antibody autoimmune responses associated with each major cardiovascular diseases;
  2. use MHC tetra-mers or similar techniques to characterize T cell autoimmune responses associated with each major cardiovascular diseases;
  3. determine autoantigen repertoire changes in patients' responses to current therapies, especially therapies with immune modulating effects;
  4. develop autoantigens-based immune therapies for clinical trials

Name of idea submitter and other team members who worked on this idea Professor Xiaofeng Yang, MD, PhD, Professor Hong Wang, MD, PhD, Professor Klaus Ley, MD

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26 net votes
28 up votes
2 down votes
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Goal 2: Reduce Human Disease

Biology of the intact alveolar wall – the new frontier in lung research

HOW DO WE STUDY THE BIOLOGY OF THE INTACT ALVEOLAR WALL IN THE CONTEXT OF LUNG DISEASE AND REPAIR?

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

Details on the impact of addressing this CQ or CC

SEE UPLOADED FILE

Feasibility and challenges of addressing this CQ or CC

SEE UPLOADED FILE

Name of idea submitter and other team members who worked on this idea JAHAR BHATTACHARYA

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2 net votes
2 up votes
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Goal 4: Develop Workforce and Resources

Suipport new research using the R21 mechanism

The decision by NHLBI to not support the R21 mechanism may be stifling new and innovative research, partcularly by young investigators who do not have a track record of R01 funding. The critical challenge is to keep funding new ideas from younger investigators to keep their careers viable while they obtain the data and publications necessary for further R01-level funding.

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 state of NHLBI funding rates for R01s are so low that we are undoubtedly loosing many young researchers as the fail to obtain adequate support for their research. Funding R21 grants will allow new, innovative, and perhps risky projects to proceed, while keeping less established researchers in the field. Re-establishing R21 funding may prevent the impression that NHLBI is more interested in supporting established labs and not advocating for and supporting new investigators.

Feasibility and challenges of addressing this CQ or CC

Given the limited budget of R21s, they will not have as large an impact on the overall budget of NHLBI as the equivalent number of funded R01 grants. Therefore, this change is feasible from a financial standpoint. Obviously, funding R21s will decrease funding for other mechanisms. Finally, it is possible that many of these grants will not lead to advances in the field, but it is my understanding that studies show the same thing about R01s.

Name of idea submitter and other team members who worked on this idea George Porter

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87 net votes
101 up votes
14 down votes
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Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease

Do SCD patients with hemodynamics consistent with pulmonary arterial hypertension (PAH) respond to medications designed to treat PAH?

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

Details on the impact of addressing this CQ or CC

What is known about this topic:

  1. Case series have demonstrated potential therapeutic benefits for endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostacyclins in PH of SCD patients
  2. Three attempted randomized placebo controlled trials of these agents in SCD patients have not gone to completion and, as a result, were under-powered to demonstrate efficacy.
  3. Sildenafil produced an increase in hospitalization for pain crises in this population.
  4. Anecdotally, select SCD patients with PAH have hemodynamic and clinical benefits from PAH medications.
  5. Approximately ½ of PH in SCD patients have some degree of pulmonary venous hypertension and these medications may not be helpful here.
Feasibility and challenges of addressing this CQ or CC

Areas of controversy:

  1. Only one of the three randomized controlled trials required a PAH diagnosis prior to randomization, so the actual question hasn’t been properly addressed.
  2. SCD patients with PAH are different than idiopathic PAH patients in terms of their underlying disease, so possibly the treatment response is different.
  3. What are the right clinical trial endpoints for this population?
  4. What is the role of SCD specific therapy (hydroxyurea, transfusions) in treating PAH of SCD?
  5. How can investigators design a clinical trial which allows for enough patient accrual to achieve its endpoints?
  6. What novel therapies can be developed to treat this population?
  7. What unrecognized medication toxicities are SCD patients at increased risk for?

Name of idea submitter and other team members who worked on this idea ATS Member

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3 net votes
3 up votes
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Goal 2: Reduce Human Disease

A Program of Research in the Prevention of Chronic Heart Failure

There is a need to address chronic heart failure (HF) through improved identification of patients at risk for HF and of patients with pathological ventricular remodeling who have minimal evidence of clinical HF, and more focused and individualized pharmacologic and lifestyle treatments and monitoring of patients with HF risk. Approaches would include big data collection, omics, statistical modeling, and focused clinical... 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

Substantially reduce the age-adjusted incidence and population burden of chronic heart failure.

Feasibility and challenges of addressing this CQ or CC

The big data and omics revolutions have made it feasible to collect and analyze a variety of data in large numbers of persons within a relatively short time. A very large sample size provides excellent statistical power. Also, the public health and economic magnitude of the problem create the urgency needed to address the critical challenge expeditiously.
Chronic heart failure (HF) is easily the most common and growing cardiovascular cause of hospitalization and impaired functional status and quality of life in the U.S. and much of the world. This is the case despite improved pharmacologic and lifestyle treatment of HF, as well as improved control of blood pressure in the general population. While some HF in the very elderly may reflect the aging process, the epidemiology suggests that most incident cases could be prevented or postponed for years. Also, there are major ethnic and socioeconomic disparities in the incidence of HF.

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

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17 net votes
28 up votes
11 down votes
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Goal 3: Advance Translational Research

Translation Research Dissemination & Implementation Frameworks

We need to identify and test the proven effective dissemination and implementation frameworks that are relevant to heart, lung, and blood disorders in order to scale up evidence-based interventions in real world settings, ultimately improving health equity among minority populations, including low income minority residents living in public housing.

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

Details on the impact of addressing this CQ or CC

• Ability to determine how much of an evidence based intervention can be sustained in real world settings.
• Add utilization of D&I frameworks to researcher’s core competency training skills.
• Promote long term sustainability of evidence based interventions.

Feasibility and challenges of addressing this CQ or CC

• Researchers from the 2014 NIH’s Annual Conference on the Science of Dissemination and Implementation: Transforming Health Systems to Optimize Individual and Population Health presented compelling evidence that dissemination and implementation frameworks are an effective means to scaling up evidence based interventions.

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

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4 net votes
13 up votes
9 down votes
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Goal 3: Advance Translational Research

Screening the work force for genetic arrhythmias

Is anyone in your family at risk for a potentially lethal genetic arrhythmia? 4000 young people die each year because they bear a genetic mutation that makes them susceptible to a sudden fatal arrhythmia. The symptoms are easy to identify and awareness of these symptoms would help unsuspecting families.

 

It is estimated that one of these syndromes (LQTS) is 3 times more common in the US than childhood leukemia.

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

Details on the impact of addressing this CQ or CC

There are 3 simple warning signs for families bearing dominant mutations that could lead to arrhythmia and sudden death. These are unexplained fainting or seizure during exercise or startle, an unexplained sudden death of a young family member, chest pain and/or shortness of breath during exercise. A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias.

Feasibility and challenges of addressing this CQ or CC

A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias. Such potential patients could then be further screening by a EKG and a consult with a cardiologist.

Name of idea submitter and other team members who worked on this idea Andy Golden

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-10 net votes
2 up votes
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Goal 2: Reduce Human Disease

Neuroendocrine system in heart and lung disease

What is the role of the non-neuronal neuroendocrine system in lung and heart pathophysiological processes, and can it be targeted for lung diseases therapies?

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

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

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3 net votes
13 up votes
10 down votes
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Goal 4: Develop Workforce and Resources

Research training to support population-focused obesity research in ethnic minority populations

NIH is already facing a challenge in increasing the number and viability of researchers of color. Obesity research in black (or other high risk minority) populations can be used to explore how research training programs that focus on specific issues of importance to populations of color might contribute to the recruitment and success of ethnic minority researchers in the NIH system.

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

Details on the impact of addressing this CQ or CC

To say the least, not all researchers of color study disparities related issues and not all disparities research is done by researchers of color. That is the way it should be. However, I suspect that research focusing on populations of color would attract a greater than average proportion of researchers of color (NIMHD might have data on this but NIMHD funding alone would be grossly insufficient as the only relevant funding stream. It would also be inappropriate and ineffective to silo the entire burden as an NIMHD responsibility).

Feasibility and challenges of addressing this CQ or CC

The infrastructure for such training might not exist. Isolated minority researchers attached to various centers and programs would not necessarily work; some sort of networking would have to be done based on an infrastructure devoted to population-oriented obesity research and with a critical mass of obesity researchers focusing on the black (or other) population..

Name of idea submitter and other team members who worked on this idea Shiriki Kumanyika, Melicia Whitt-Glover, Debra Haire-Joshu

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6 net votes
6 up votes
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Goal 3: Advance Translational Research

Direct Upregulation of Antioxidant Defenses as a Therapeutic Strategy

Clinical trials involving administration of antioxidants such as vitamin C or vitamin E as therapeutic strategies for cardiovascular diseases associated with oxidant stress have proven to be surprisingly disappointing. A particularly attractive alternative approach is direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches. NRF2 is a master antioxidant and cell protective transcription... 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

Direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches will avoid the well known caveats of drug-based approaches such as off target effects and detrimental side effects. Dietary supplements such as Protandim are already available; and beneficial effects of other NRF2 up-regulators such as resveratrol and sulforaphane are beginning to be recognized. The dietary approach is minimally invasive and has high preventative value.

Feasibility and challenges of addressing this CQ or CC

Addressing this CQ is clearly feasible, as dietary supplements are currently available for humans, and the beneficial effects of foods containing compounds that upregulate the NRF2 system, e.g., broccoli, cauliflower, red wine, and grape juice are currently recognized. One challenge in addressing this question in animal models to date is that the only genetic model lacking NRF2 is a knockout mouse model, which have substantial limitations for in vivo physiological studies due to their small size. However, a recent R21 grant (#1R21OD018309-J. H. Lombard, P.I.) has allowed the development of a NRF2 knockout rat model which is better suited for physiological studies than the mouse model. In addition, the techniques used to develop the NRF2 knockout rat can be applied to multiple disease-sensitized strains, e.g., the Dahl salt-sensitive rat. Fawn Hooded Hypertensive rat, Obese Zucker rat, etc. Similar disease sensitized rodent genetic strains are not available in mice.

Name of idea submitter and other team members who worked on this idea Julian H. Lombard

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-5 net votes
2 up votes
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Goal 2: Reduce Human Disease

Optimizing Utilization of Composite and Repeat Endpoints in RCT

The use of win-ratio and other new statistical methods to analyze endpoints in new and existing clinical trials.

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

Details on the impact of addressing this CQ or CC

It could enable trials to be powered with smaller sample sizes. It can also be used to combine diverse information in a way to better guide clinical decisions.

Feasibility and challenges of addressing this CQ or CC

The methodology exists and the need is growing as we try to sort out smaller treatment effects and our focus shifts from MI (which is fairly easy to define) to heart failure (which is more nebulous).
Traditional time-to-first endpoint analyses of clinical trials fail to capture the full impact of treatment in diseases with recurring endpoints (like heart failure hospitalization) or to capture the net benefit/risk of treatments with significant opposing effects (like the anti-thrombotic pro-bleeding effects of drugs like warfarin and dabigatran in atrial fibrillation or dual anti-platelet therapy after cardiovascular stenting), New statistical methods like the (win-ratio) when used together with patient- and clinician-based rankings of the importance of possible outcomes might provide a quantitative way to optimize the relevance of trials with multiple diverse endpoints to practical clinical decision making. I propose to encourage the use of these and other similar methodologies to analyze endpoints in new and existing trials. It would require a paradigm shift in how trialists look at endpoint data and in how regulators interpret trials.

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

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-3 net votes
10 up votes
13 down votes
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Goal 3: Advance Translational Research

Developing adherence research to reduce unnecessary mobility/mortality/cost

From Cochrane Review NOV 20 2014
RB Haynes

“It is uncertain how medicine adherence can consistently be improved so that the full health benefits of medicines can be realized. We need more advanced methods for researching ways to improve medicine adherence, including better interventions, better ways of measuring adherence, and studies that include sufficient patients to draw conclusions on clinically important effects.”... 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

Effective medication exists to prevent or control most chronic diseases. The problem is that patients do not follow medical recommendations for a myriad of reasons. UNNECESSARY mortality, morbidity, poor quality of life and cost are the result of nonadherence. Intensive systematic research over a decade is the key to address the proposed challenge.

Feasibility and challenges of addressing this CQ or CC

I have developed an hypothesis, currently being examined in a controlled study by NIHLBI, that merits further evaluation. One component(J Allergy Clin Immunol: In Practice 2013;1:23) is objective measuring of asthma patients with MDI electronic monitors that need technological improvement (battery life, measure inspiration). Patients evaluated in emergency department for most chronic diseases can be objectively evaluated for adherence by assays of medication that currently are available since they exist and necessary for medication to be approved by the FDA. Other components include: coordinated identification of patient barriers; application of clinical decision support strategies to specific barriers identified; patient-centered communication skills to deliver strategies in one delivery system. Many other interventions by other researchers may also be considered during the decade.

Name of idea submitter and other team members who worked on this idea Andrew Weinstein and Asthma and Allergy Foundation of America

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5 net votes
7 up votes
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Goal 3: Advance Translational Research

Unconventional beliefs and negative attitudes to 'smart' asthma therapy

Systematically examine the contribution of unconventional beliefs and negative attitudes to inadequate clinical outcomes for asthma.

 

Budesonide/fomoterol controller/reliever therapy ('smart' therapy) in large US studies - adults

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

Name of idea submitter and other team members who worked on this idea American Thoracic Society member

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1 net vote
1 up votes
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Goal 3: Advance Translational Research

Healthcare Inequity

Many continue to pay higher benefits for less care. Often they are seniors who do not need OB/Gyn or pediatric benefits, etc. They are not covered for eyeglasses, dental work, etc. Those covered under Obama care plans and subsidies are entitled to more care. Now states are legalizing recreational drug use, same sex marriage, etc.
Why? It is only logical to realize this will place more unnecessary burden on the already... more »

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

Name of idea submitter and other team members who worked on this idea Suzanne Michalek

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-10 net votes
5 up votes
15 down votes
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