Goal 1: Promote Human Health

Sleep Effects on Lung Biology

What sleep patterns contribute to normal lung growth, development, and metabolism from birth through childhood, lung health during middle-age, and senescence of lung tissues in the elderly?

Submitted by (@nhlbiforumadministrator)

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
16 up votes
13 down votes
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Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the relationship of ChILD disorders to adult diffuse lung disease?

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

This would need to be addressed in the context of databases such as those for familial idiopathic pulmonary fibrosis (F-IPF) or IPF clinical trials, as well as perhaps databases for COPD and pulmonary hypertension. What is the prevalence and spectrum of childhood respiratory disease in family members within these cohorts? What is the prevalence of adult lung disease in family members in ChILD registries? In disorders such as surfactant-related sequence variants, which can cause disease across the lifespan, what are likely “2nd hits”, genomic or environmental, that may lead to clinical disease at particular ages/developmental stages?

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

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2 net votes
2 up votes
0 down votes
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Goal 2: Reduce Human Disease

The role of Extracorporeal Photopheresis (ECP) in the prevention and treatment of rejection of heart and lung transplants

According to the ISHLT, more than 4,000 patients undergo a heart transplant each year, and almost 4,000 receive single or double lung transplants. Their prognosis depends heavily on the avoidance of rejection, which claims the majority of their lives. For heart transplant recipients, the median survival is 11 years, while for lung transplant recipients, it is approximately 5 years. The current most common anti-rejection ...more »

Submitted by (@mmarques)

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

Details on the impact of addressing this CQ or CC :

Patients who are fortunate to receive a matched heart or one or two lungs transplants are at high risk of dying from rejection early and even years after the operation. Thus, they are given cocktails of highly toxic anti-rejection drugs for the rest of their lives. Unfortunately, despite compliance with their drug regimens, many patients still suffer repeated episodes of rejection that may be fatal. In addition, they develop serious side-effects such as diabetes, infections, malignancies, renal failure, etc. ECP has been shown efficacy in preventing and treating cardiac transplant rejection, but the data are limited. ECP appears to benefit such patients by causing an increase in the number of circulating T regulatory (“T regs”) cells. T regs are known to mediate immune tolerance, the ultimate goal of a long-term successful transplant. The role of ECP in lung transplantation is mostly unknown. Very preliminary data have been gathered from retrospective studies. We suspect that patients with early bronchiolitis obliterans syndrome (“BOS”) will benefit from ECP prior to developing irreversible pulmonary damage. In both types of transplants, however, it is unknown when should ECP be started, how often it should be employed (treatment schedule), and for how long. Finally, the most compelling argument to use ECP in heart and lung transplantation is its excellent side-effect profile. Furthermore, ECP may allow a decrease in the number of drugs needed to prevent rejection.

Feasibility and challenges of addressing this CQ or CC :

Many patients with heart and lung transplants develop severe and often fatal rejection despite the current drug options to prevent rejection. ECP could be added to their treatment regimens and decrease side-effects, improving long-term survival.

 

ECP is generally well tolerated and complications are extremely infrequent.

 

There is a great potential for multi-disciplinary collaboration between Apheresis Medicine, Cardiology, and Pulmonary specialists.

 

It is conceivable that manufacturers of ECP instruments will be interested in contributing to the design and support of these studies.

 

Such studies could shed light in the mechanism of action of ECP in heart and lung transplantation.

 

There is a need to develop standardized treatment regimens based on well designed clinical trials to further optimize the use of ECP. Development and standardization of measurable outcomes is critical for the success of clinical studies in apheresis in general, and ECP in particular.

 

Challenges:

1. Limited number of institutions providing ECP treatment.

2. Cost of ECP procedures.

3. Small number of animal models available for apheresis research. Thus, limited studies of ECP mechanism(s) of action. However, understanding pathological mechanisms and their relationship to response to apheresis is critical for optimization and advancement of patient care in heart and lung transplantation.

4. Lack of infra-structure for apheresis research.

Name of idea submitter and other team members who worked on this idea : Marisa Marques on behalf of ASFA

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80 net votes
102 up votes
22 down votes
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Goal 1: Promote Human Health

Injury, regeneration and repair of the developing lung

Understanding injury, regeneration and repair of the developing lung.

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 :

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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0 net votes
1 up votes
1 down votes
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Goal 3: Advance Translational Research

Leveraging big data for T4 translation research

What approaches can help leverage the emerging big data in health and health care for observational and interventional implementation research in heart, lung, blood, sleep diseases?

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 :

• Integration of big data analytics into T4 research study design and interventions development

• Innovative linkages across multiple health and non-health sector data

• Innovative methods to analyze big data linked across sectors

• Various communities are using big data analytics to understand population health data (e.g. electronic medical records s) and opportunities exist for consolidation of these efforts and standardization of methodologies

Feasibility and challenges of addressing this CQ or CC :

• NIH now has focus on big data in its formative stages

• Significant amount of NIH’s budget is/will be dedicated to big data research

• NHLBI can leverage NIH’s investment by foster research in D&I big data analytics and systems science

• Future investment in big data should yield opportunities and focus efforts

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

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0 net votes
16 up votes
16 down votes
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Goal 2: Reduce Human Disease

Systemic manifestations and co‐morbidities of chronic lung disease

More emphasis must be placed on systemic manifestations and co‐morbidities of chronic lung disease such as depression, oral disease and heart disease.

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 :

Management of multiple comorbidities: Health care delivery is undergoing reform to improve

efficiency and reduce costs. At present subspecialists are generally adept at managing a narrow aspect

of an individual’s health but less commonly is a practitioner able to provide comprehensive

management of people with multiple comorbidities. Indeed, many clinical trials are performed in highly

selected cohorts yielding important results but frequently lacking the generalizability to be applied to

many of our patients. Thus, we would support efforts to optimize the design of clinical trials to be more

applicable to heterogeneous groups including elderly, people with chronic diseases, and patients

receiving multiple medications.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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1 net vote
1 up votes
0 down votes
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Goal 1: Promote Human Health

Critical Windows in Early Development to Maximize Lung Health

Is there a critical window of growth and development for maximizing lung function?

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 :

Low lung function during childhood tracks to early adulthood and contributes to early onset disease. Lung health promotion is needed, but we know little about what can enhance and protect human health during rapid phases of lung development in utero and growth postnatally to adulthood.

Feasibility and challenges of addressing this CQ or CC :

Researchers could turn their attention on healthy and “maximally” health populations (human and model organisms) to understand genetic and environmental exposures that influence lung function at upper ends of the spectrum (>2 SD from the mean).

Recent findings suggest that there is an urban-rural continuum of lung function in specific ethnic groups; and interventions with maternal dietary supplements can enhance lung function in offspring. These set the stage for further study on developing knowledge of early life events that can inform lung health promotion.

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5 net votes
17 up votes
12 down votes
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Goal 1: Promote Human Health

Role of the lymphatic system in heart, lung, blood, sleep health and diseases

What is the role of lymphatic system in normal function of the heart? Do dysfunctional lymphatics contribute to heart failure? Do lymphatics have a role in recovery after MI? It has been reported that lymphatic vasculature transport HDL during reverse cholesterol transfer. Do lymphatics have a role in atherosclerosis? What is the contribution of lymphatic system to asthma or COPD? Does the lymphatic system contribute ...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 :

Understanding how lymphatic system contributes to normal physiology of heart, lung, blood, sleep systems will help also lead to new approaches for treatment of heart, lung, blood, sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Basic understanding of the development and hemodynamics of the lymphatic system and reagents to study the lymphatic function are available.

Lymphatic vasculature is essential for fluid hemostasis in the body, collects and returns the protein- and lipid-rich interstitial fluid to blood circulation, and also involved in immune cell trafficking and inflammation. Given these important physiological roles, function of the lymphatic system is expected to contribute to normal physiology of organs and its dysfunction to major diseases. There is very little or no information how the lymphatic system contribute to health and diseases of the cardiovascular, pulmonary and blood systems, and there are many unanswered questions. Answers to these questions may lead to new approaches for treatment of major HLB diseases. Main challenge is to get heart, lung, blood, sleep investigators interested in studying the contribution of the lymphatic system to heart, lung, blood, sleep health and diseases.

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

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50 net votes
77 up votes
27 down votes
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Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood diseases?

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 :

Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC :

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.

Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

 

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

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

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94 net votes
122 up votes
28 down votes
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Goal 1: Promote Human Health

Lung Repair and Regeneration

What characteristics define progenitor lung cell niches? What controls proliferation and differentiation of lung progenitor cells in normal repair? Can endogenous repair mechanisms and alterations of progenitor cell cycle be harnessed to promote regeneration?

Submitted by (@nhlbiforumadministrator)

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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10 net votes
22 up votes
12 down votes
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Goal 3: Advance Translational Research

Developing animal models of lung transplantation.

Lung transplantation as a cure for terminal lung disease has seen little improvement in outcomes for more than 20 years. The field remains highly challenging, in part, because of an absence of robust animal models which are technically- feasible and reproducible across centers. Further, models have limited relevance to clinical (chronic) airway remodeling, the leading problem in pulmonary allografts. In the absence of ...more »

Submitted by (@mnicolls)

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 critical challenge is to address the leading problems facing lung transplant patients through the creative application of multiple technological platforms employing all available pre-clinical models by multiple NIH investigators. With greater focus on the deeper development of existent models, the delineation of their strengths and limitations and importantly, cooperation between Academic Centers, efforts can be optimized to improve outcomes for a condition that has enjoyed little benefit from basic research.

Feasibility and challenges of addressing this CQ or CC :

The siloed nature of much clinical and experimental lung transplantation research limits progress and broader initiatives. With specific respect to developing animal models of lung transplantation, the general lack of consensus about the suitability of the techniques employed at different institutions stifles progress. A strategic vision, guided by leaders across the field, highlighting benefits and limitations of current animal models can be coupled with a consensus statement about the most pressing issues in lung transplantation worthy of increased investigation.

Name of idea submitter and other team members who worked on this idea : Mark Nicolls

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5 net votes
15 up votes
10 down votes
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