Goal 2: Reduce Human Disease

Balancing Risks and Benefits: How Do Clinical Guidelines in Cardiovascular Medicine Promote the Health of an Individual?

Much of the hopes for precision medicine (as outlined Dr. Dr. Collins) are based on deriving large amounts of genomic, proteomic, epigenomic and metabolomic data on large cohorts of patients. It will take decades to build these cohorts and even more time to analyze them and derive specific conclusions on how these will help individualize treatments. However, there is a pressing need for how to individualize contemporary ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

 

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

 

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

 

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

 

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

 

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

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

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Goal 2: Reduce Human Disease

The importance of cosidering sex and gender in presicion medicine

Precision medicine will be invested in across NIH, as per the President's "Precision Medicine Initiative". It is critical that the population base be reflective of the US population, including 50% women. Gender, especially as it relates to exposures, must be a dominant consideration, as these factors are critical to the development of human disease and therefore will be important to prevention.

Submitted by (@pajohnson)

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

Details on the impact of addressing this CQ or CC :

Precision medicine that can be applied accurately to different groups within o our population, in particular women and racial and ethnic minorities.

Feasibility and challenges of addressing this CQ or CC :

Achieving this goal is feasible and essential.

Name of idea submitter and other team members who worked on this idea : Paula Johnson

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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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Goal 2: Reduce Human Disease

Basic Research & Precision Medicine

How can NHLBI best encourage basic research areas that are critical to the development of precision medicine approaches for lung disease?

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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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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Goal 3: Advance Translational Research

Durable gene activity map at the individual level

A durable gene activity map of the individual to understand when certain gene sets are on vs off or dysfunctional over an individual’s lifetime as one way of guiding the precision of medicine for that patient. It would need to be person portable and universally exportable and interpretable across all of the EHRs.

Submitted by (@greg.martin)

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 : Society of Critical Care Medicine Executive Committee/Council

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Goal 2: Reduce Human Disease

Consequences of drug interactions leading to QTc prolongation

Better understand the consequences of drug interactions leading to QTc prolongation. About 1/3 of cardiac ICU patients develop QT prolongation and about 45% receive drugs that are possibly contributing to this problem. The full spectrum of contributors and causes, as well as the patient-centered and health-system-centered clinical outcomes, are not known.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Reduction in adverse drug events and preventable deaths

Feasibility and challenges of addressing this CQ or CC :

Combining the power of predictive analytics of high dimensional data streaming continuously from critically ill patients, combined with precision medicine genomics and metabolomics, makes this imminently feasible.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Council

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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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Goal 1: Promote Human Health

Predictive analytics to engage healthy behaviors and maintain health while reducing cost

Predictive Health employs the principle that using modern health testing and predictive analytics will better define true health (not just absence of disease) and, in combination with large-scale data analytics, will facilitate predicting deviations from the healthy trajectory earlier than traditional disease diagnosis, thus allowing more effective and less costly interventions to maintain health. Predictive Health educates ...more »

Submitted by (@greg.martin)

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 addressing this CC the health of the nation will be improved: better national and individual understanding of health, greater longevity of sustained health and productivity, reduced costs of healthcare by focusing on health than on disease diagnosis and management.

Feasibility and challenges of addressing this CQ or CC :

The Emory/Georgia Tech Predictive Health Institute (http://predictivehealth.emory.edu) was founded ~10 years ago by launching educational (http://predictivehealth.emory.edu/education/index.html) and scientific (http://predictivehealth.emory.edu/chd/index.html) programs to achieve the Predictive Health goals. The scientific approach created a prospective longitudinal cohort of individuals who have been richly phenotyped according to traditional medical testing (clinical laboratory, stress testing, etc) and research testing (genomics, metabolomics, regenerative cell potential, oxidative stress) to create the deepest understanding of current and future health. The success of the Predictive Health Institute demonstrates the feasibility and potential success of such a critical challenge to both human health and healthcare expenditures.

Name of idea submitter and other team members who worked on this idea : Greg Martin, for the Emory/Georgia Tech Predictive Health Institute

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Goal 2: Reduce Human Disease

Precision medicine in non-malignant lung diseases

NIH has a major initiative in Precision Medicine, including whole genome sequencing. In contrast to cancer, mutations with large clinical effects are expected to be uncommon in most non-malignant chronic diseases, such as asthma and COPD. Other data types such as gene expression, biomarkers, and micro RNAs must be combined with clinical and imaging phenotyping to advance Precision medicine in non-malignant lung diseases. ...more »

Submitted by (@craighersh)

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 goal is to combine clinical and molecular data to identify subtypes of patients within the major chronic respiratory diseases. Understanding molecular pathways will first lead to more appropriate drug repositioning and eventually novel drug development.

Feasibility and challenges of addressing this CQ or CC :

NHLBI has many cohorts of subjects with chronic lung diseases with longitudinal clinical characterization, many with banked biospecimens. It is quite feasible to perform genomic, epigenetic and biomarker assays on these specimens. Based on these results, hypothesis-based targeted profiling can be done in prospective studies.

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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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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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