Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

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 :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

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

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32 net votes
50 up votes
18 down votes
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Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

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 :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

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

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

Study on key product factors for optimal Bone Marrow Transplantation (BMT) graft function

Hematopoietic progenitor cells (HPC) collected by Apheresis is the most common source used for BMT. How the cells are collected and what kinds of cells are collected can affect BMT graft function. Limited studies have been done to study the key product factors in relationship to optimal graft function. Questions remain such as the optimal lymphocytes contents for reduced infection post BMT, optimal megakaryocyte precursor ...more »

Submitted by (@yanyunw)

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

Details on the impact of addressing this CQ or CC :

Optimal cell therapy products can lead to reduced post BMT complication and reduced morbidity and mortality.

Feasibility and challenges of addressing this CQ or CC :

In vitro, animal studies, clinical samples can be used for key product factors for optimal BMT graft function.

These can be achieved if funding is available, as there are many centers perform allo and auto BMT.

Funding support is critically needed in this area.

Name of idea submitter and other team members who worked on this idea : Yanyun Wu on behalf of ASFA

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70 net votes
93 up votes
23 down votes
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Goal 1: Promote Human Health

Qigong and Tai Chi for Chronic Disease Prevention

Non-pharmacological interventions for pain and stress have gained tremendous momentum. Mind-Body Practice -- Qigong and Tai Chi -- are group based and inexpensive to implement. The evidence base suggests that these practices are safe and effective for a multitude of preventable chronic disorders.. THE QUESTION: Given safety and efficacy, should there be vigorous research on implementation of Qigong and Tai Chi and ...more »

Submitted by (@rogerjahnke)

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 can we do to assure that safe, effective, inexpensive non-parmacological approaches like Qigong and Tai Chi become widely diffused into communities, agencies, organizations, schools, health systems and businesses.

Feasibility and challenges of addressing this CQ or CC :

We have participated in a number of studies that have contributed to the evidence base for Mind-Body Practice as a safe and effective non-pharmacological programming.

 

The key -- group based. For the financing, group based is inexpensive. For the efficacy group based supports compliance.

Name of idea submitter and other team members who worked on this idea : Dr Roger Jahnke, http://IIQTC.org

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2 net votes
33 up votes
31 down votes
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Goal 3: Advance Translational Research

ESTABLISHMENT OF APHERESIS MEDICINE CONSORTIUM TO ADVANCE DEVELOPMENT OF EVIDENCE BASED THERAPIES

The apheresis medicine encompasses treatment of numerous diseases many of which are directly related to blood, lung and heart. There is a need to establish consortia for Apheresis Medicine to facilitate networking, information exchange and research collaboration among investigators, including junior investigators. These consortia would perform basic science as well as translational research and investigate the best pathways ...more »

Submitted by (@zbigniew.m.szczepiorkowski)

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 creation of one or more Research Consortia devoted to research in Apheresis Medicine would allow for the establishment and support of a core group of investigators and institutions representing key specialty areas across the spectrum of Apheresis Medicine. An initial focus would be translational research priorities. In addition, we believe that a strong U.S. based consortium would facilitate participation of international investigators and societies, which would improve patient accrual on studies, especially those patients with rare disorders or who have rare indications for apheresis therapy. Such a group would significantly enhance the likelihood of completing high quality studies.

 

There is increasing national interest in developing new registries, bio-repositories and data-repositories. Very often such efforts do not include information regarding apheresis nor do they consider apheresis information as being important data points. A centralized, well organized and sustainable registry, either established and/or new for Apheresis Medicine, would be of great value to study the outcomes of therapeutic apheresis for different disease conditions. This need is particularly relevant for rare disorders and rare indications, for which a pilot effort is already being undertaken and sponsored by ASFA- the American Society for Apheresis.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: There are hundreds of thousands apheresis procedures performed each year in the US. Many of these procedures are performed in tertiary and quaternary academic medical centers. These centers have experience in education, basic science, translational research and clinical trials. Despite the low frequency of some diseases there is a real possibility of performing clinical trials in the context of multicenter consortium. Such consortium could also assist in development of new projects related to Apheresis Medicine (both basic science and clinical) which then can proceed to clinical trials quickly as the appropriate infrastructure will be created within the consortium. This infrastructure would also serve education of the new investigators.

Challenges: Standardization of approaches between different medical centers might be initially difficult, but as it has been shown many centers follow in their clinical practice ASFA designated indications. Setting up research priorities for the consortium might be challenging as well as accrual patients to clinical trials within the consortium. Though standardization of the apheresis devices is not feasible, this could be mitigated by appropriate study designs. The number of investigators in apheresis medicine is limited but the consortium may serve as a great platform to expand its numbers through collaborative efforts of involved centers.

Name of idea submitter and other team members who worked on this idea : Zbigniew M. Szczepiorkowski, Yanyun Wu on behalf of ASFA

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112 net votes
131 up votes
19 down votes
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Goal 4: Develop Workforce and Resources

DEVELOPMENT AND SUPPORT FOR APHERESIS MEDICINE INVESTIGATORS

The apheresis medicine encompasses treatment of numerous diseases many of which are directly related to blood, lung and heart. However, there are very limited opportunities for training young investigators in basic and translational research related to Apheresis Medicine. There is a need to promote Apheresis Medicine as a viable field of research for junior and established investigators. The influx of well-trained junior ...more »

Submitted by (@zbigniew.m.szczepiorkowski)

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

Details on the impact of addressing this CQ or CC :

Therapeutic apheresis is the process of transiently removing whole blood from the body, separating it into various components (e.g., cells, plasma, proteins, antibodies, antigen-antibody complexes, lipids, etc.), removing those components that contribute to disease, and then returning the remaining blood with possible addition of a blood component to the body.

 

Hundreds of thousands of apheresis procedures are being performed every year in the US. Many of these procedures are life-savings while others are likely to be of limited benefit to patients and healthcare system at large. There is lack of good understanding pertaining to basic mechanisms of apheresis and optimal ways of applying apheresis to the improvement of underlying conditions as well as to the ability of apheresis to enhance other treatment modalities. This in turn is caused by significant shortage of well-educated and trained physician scientists willing to address basic science and translational-clinical questions related to applications of apheresis in clinical practice.

 

Currently there are no specific mechanisms for training such individuals. Utilization of and integration with existing educational/training programs, such as T32 grants, K23/K24/K25 grants, institutional K12 awards and CTSA educational programs would likely result in the cadre of junior investigators who can tackle questions related to basic mechanisms as well as clinical approaches to treating diseases using apheresis strategies.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: Incorporation of apheresis medicine training into currently available resources is likely to be highly feasible. This training can be provided across many medical specialties including hematology, transfusion medicine, cardiology, pulmonology and others. Inclusion of basic scientists involved in research of blood disorders, lung and heart disorders, as well as immunology will expand the outreach. Identification of individuals interested in pursuing research in apheresis medicine might be accomplished on different levels of training starting with medical school, internship, residency and fellowship as well as early years of medical career in a variety of medical specialties.

 

Challenges: The primary challenge is related to perception. Apheresis has an undeserved reputation as an "old" science; one that in recent years has been overtaken at times by newer medical treatments. Yet it still is the only and often life-saving treatment for certain conditions. Apheresis remains the go-to procedure for treating many common and rare maladies alike, such as TTP, and new treatment indications are being added. Although many specialists like hematologists, neurologists, nephrologists see the evidence and benefits of therapeutic apheresis in their everyday work, the progress of Apheresis Medicine as a medical specialty has been generally slow. The other major challenge is lack of funding of basic research and translational research related to Apheresis Medicine.

Name of idea submitter and other team members who worked on this idea : Zbigniew M. Szczepiorkowski, Yanyun Wu on behalf of ASFA

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108 net votes
127 up votes
19 down votes
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Goal 2: Reduce Human Disease

Influence of the Gut Microbiome on Pulmonary Immunity in HIV-Infected Individuals

It has become increasingly clear that gut microbiota have a tremendous impact on human health and disease. While it is well known that commensal gut bacteria are crucial in maintaining immune homeostasis in the intestine, there is also evidence of indirect effects on the lung. Multiple studies have shown that alterations in gut microbiota can lead to severe defects in pulmonary immune responses and reduced ability to ...more »

Submitted by (@brent.palmer)

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

Details on the impact of addressing this CQ or CC :

HIV-infected individuals are at significant risk of developing and dying from infectious and non-infectious pulmonary complications. Alteration of gut microbiota have been shown to have dramatic effects on pulmonary immunity and severity of lung infections. For instance, multiple studies have indicated that probiotic treatment with certain Lactobacillus and Bifidobacterium strains results in reduced incidence and severity of upper respiratory tract infections in children. Similarly, a recent study showed that treatment with the minimally absorbed antibiotic neomycin was associated with alterations in gut microbiota composition and concomitant reduced pulmonary immunity and the inability to control Influenza infection in mice. It was recently described that HIV infection is associated with a dramatic alteration in gut microbiota and that these changes persist with antiretroviral therapy (ART). Thus, it is important to understand how these alterations may effect lung immunity, since the majority of HIV-infected individuals develop pulmonary infections. Furthermore, gut microbiota contribute to development of non-infectious complications such as atherosclerosis, metabolic disease, obesity and diabetes. It is thus highly plausible that the gut microbiota may also play a role in the development of non-infectious complications of the lung such as Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension, the rates of which are elevated in HIV-infected individuals.

Feasibility and challenges of addressing this CQ or CC :

A better understanding of how alterations in gut microbiota associated with HIV infection affects pulmonary infectious and noninfectious complication could lead to therapies to protect this “at risk” group. Furthermore, manipulation of the gut microbiota in HIV-infected individuals using pro- and/or pre-biotics, antibiotics or diet modification to a composition that is associated with increased pulmonary immunity, reduced infections and lung complications are all low risk therapeutic strategies that could substantially improve lung heath in these individuals.

Name of idea submitter and other team members who worked on this idea : Brent Palmer (NHLBI-INHALD group member) and Catherine Lozupone

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3 net votes
7 up votes
4 down votes
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Goal 1: Promote Human Health

New technologies for Personalized health monitoring: too much or not enough

The development of personalized medicine and the increasing amount of information extracted from individual and patients throughout their life is expected to growth significantly. Multiple types of physiological sensors are currently embedded in everyday-life objects and yet their clinical value and their potential to improve health care is not well defined. It seems fundamental that the NIH develops a core research group/ ...more »

Submitted by (@heartjpc)

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 impact of this compelling question would promote the development of the right technologies for monitoring physiological signals at long-term. Also, this question should be addressed in collaboration with other federal agencies and institutes such as the NSF and the FDA. Both these agencies are currently supporting and reviewing new-long term technologies but the understanding of the impact of these novel techniques remains to be studied.

Feasibility and challenges of addressing this CQ or CC :

none

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

Efficient Evidence-Based Practice

How can we most efficiently utilize limited resources/manpower to facilitate adherence to evidence-based practices and enhance public health?

Submitted by (@nhlbiforumadministrator1)

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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5 net votes
14 up votes
9 down votes
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Goal 2: Reduce Human Disease

What is the optimal treatment goal for hypertension?

In adults without diastolic hypertension (DBP ≥ 90 mm Hg), what is the best way to determine at what systolic blood pressure should treatment be initiated?

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 :

The failure to resolve the debate about what is the appropriate goal for treatment of systolic hypertension could adversely effect the progress we have made in reducing the level of systolic blood pressure among the one third of adults with hypertension. At the heart of this debate is what is the optimal balance between lowering systolic blood pressure versus causing adverse consequences in those who are being treated for hypertension.

Feasibility and challenges of addressing this CQ or CC :

Because the existence of large clinical research networks with electronic medical records and use of generic drugs, all mean that a large pragmatic trial is definitely feasible.

Despite fifty years of clinical trial research and forty years of national guideline activity, important clinical questions remain under intense scientific debate. The importance of these questions is underlined by the scientific consensus that hypertension is the most important cardiovascular risk factor globally, in fact, more important than even tobacco use. Further hypertension research could be important because of the role of hypertension not only in CVD, but also in chronic kidney disease, stroke, and possibly in dementia and age related cognitive decline.

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

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13 net votes
28 up votes
15 down votes
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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest. Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

 

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

 

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

 

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

 

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

Name of idea submitter and other team members who worked on this idea : Jalees Rehman

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7 net votes
11 up votes
4 down votes
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Goal 3: Advance Translational Research

Addressing Unrecognized and Over Diagnosis of COPD

How can we create precision diagnostics for COPD in practice settings that will help inform the transition from screening to better diagnosis and treatment strategies and that will help identify patients or communities at highest risk for unrecognized or over diagnosed COPD.

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 :

About 12 million individuals are estimated to have undiagnosed COPD and in most cases patients aren’t diagnosed until they have lost over half of their lung function leading to worse outcomes short and long term. Conversely there are challenges with over and mis diagnosed COPD that can result in over treatment and incorrect treatment. Fine tuning screening, diagnostic and management tools can result in earlier and proper identification of disease, earlier initiation of risk mitigation and/or treatment strategies and improved health outcomes as well as improved efficiencies in the healthcare system.

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

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11 net votes
12 up votes
1 down votes
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