Showing 77 ideas for tag "lung"

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?

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

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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

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 »

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

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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

What are the mechanisms of lung injury after HCT

Despite major advances in supportive care and tissue typing non relapse mortality rates for adults undergoing hematopoietic cell transplantation are still between 15-20 % at 2 years.
Lung injury and respiratory failure is a major causes of death after HCT.
Although the BMT-CTN has a focused agenda on GVHD, reduction of lung toxicities will be important to improve outcomes.
NHLBI should encourage researched from the... 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

Discovery of mechanisms of lung injury in the HCT setting are likely to be relevant for the non HCT setting.
The BMT CTN prospectively collects data on lung toxicity on all HCT recipients on trial, samples exist in the repository that could be used for biomarker discovery.

Feasibility and challenges of addressing this CQ or CC

Main challenge is to get the two teams of investigators working together

Name of idea submitter and other team members who worked on this idea Sergio Giralt

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59 net votes
88 up votes
29 down votes
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Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

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

Details on the impact of addressing this CQ or CC

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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54 net votes
74 up votes
20 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 »

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

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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 3: Advance Translational Research

Increasing Regenerative Medical Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Current PAH therapies mainly act of the vasoconstrictive component of the disease; however there is a widely accepted view that another contributor to the disease is an abnormal overgrowth of cells that line the pulmonary arteries, which... more »

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

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In the past twenty years, 12 PAH targeted-therapies have been approved by the FDA. This increase in disease state awareness and in the treatment armamentarium have contributed to an increase in average survival from 2.8 years to an estimated 8-10 years. However, current treatments primarily address the vasoconstrictive component of the disease and do not address the now accepted theory of post-apoptotic overgrowth of hyperproliferative cells of the pulmonary vessels. A number of circulating stem and progenitor cells, derived from the bone marrow, have been identified that could have roles in repair of the pulmonary vascular system when interacting with the quickly, abnormally growing cells in the lung vessels. Work in this area has been named as a future research opportunity in the NHLBI-ORDR Strategic Plan for Lung Vascular Research (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC

Basic and translational research support is needed—including high-throughput approaches such as phage display and large-scale proteomic analysis—to better understand the relationship between circulating bone marrow-derived cells, lung-resident stem and progenitor cells, and endothelial cells of the pulmonary arterial system.

Name of idea submitter and other team members who worked on this idea Pulmonary Hyeprtension Association, Michael Gray, Katie Kroner

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71 net votes
81 up votes
10 down votes
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Goal 2: Reduce Human Disease

Exercise effects on cellular level

What cellular and/or intracellular signaling events are activated in response to acute or chronic physical activity that lead to or explain improvements in health outcomes, prevention, or treatment of lung diseases?

Which metabolic signatures induced by exercise/physical activity would be predictive/ associated with poor lung disease prognosis?

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

Research Opportunities in HLB to Facilitate Aging in Place

There is a need for greater evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung, blood, sleep conditions to remain in their private homes if feasible, if technology is utilized that fosters clinical and epidemiologic research.

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

Details on the impact of addressing this CQ or CC

No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Feasibility and challenges of addressing this CQ or CC

Evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung and blood conditions remain in their private homes is feasible if technology is utilized that fosters clinical and epidemiologic research.
Many cardiovascular risk factors increase as the population ages including uncontrolled systolic hypertension and atherosclerosis both contributing to the well-being of our society and increasingly high health care costs (Izzo, Levy, & Black, 2012). No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

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

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17 net votes
35 up votes
18 down votes
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Goal 1: Promote Human Health

Funding of Stem Cell/Lung Regeneration Research

How to "cure" a chronic, incurable disease - A potential giant step in saving the lives of many thousands of Americans, and potentially millions worldwide, who are afflicted with COPD, the third leading cause of death in the U.S.
The financial effect of COPD in the United States alone is well over $50 billion per year. It is estimated that some 30 million Americans have COPD, which of course means that at least that... more »

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

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COPD is chronic and presently incurable. Although it sickens and disables nearly 30 million Americans, and kills 140,000 of them each year, the only "cure" is a lung transplant. Due to the scarcity of organ donors and the requirements that lungs be removed from the donor in a hospital setting, only about 1,400 lung transplants are performed in the Unites States each year. Unfortunately, transplants are fraught with complications, side effects, and potential rejections, and on the average, add only about 5 years to the life of the recipient. The best potential solution lies with the stem cell and lung regeneration research that is presently occurring at a few centers around the country. Ideally, the re-engineered lungs would be composed of the patient's own stem cells, eliminating a great many of the current transplant issues.

Feasibility and challenges of addressing this CQ or CC

Research is presently in process on construction or reconstruction of human organs. There has been success in creating some of the simpler organs, such as the esophagus and bladder, and a Medical Center in Galveston has implanted re-engineered lung is a pig. As of my latest conversation with the lead Doctor on the project, results so far are promising.
There is general agreement among the researchers with whom I have communicated that we are between 5 and 20 years away from human trials of re-generated lungs using the patient's own stem cells, but more funding means more research which means more possibilities of the saving of lives.

Name of idea submitter and other team members who worked on this idea Jim Nelson - COPD Foundation MASAC/CAC/BOARD Committee Member

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25 net votes
32 up votes
7 down votes
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Goal 2: Reduce Human Disease

Impact of lung remodeling on congestive heart failure progression

End stage congestive heart failure (CHF) causes intensive lung remodeling beyond the type-2 pulmonary hypertension. CHF induced lung remodeling includes profound lung fibrosis, lung vascular remodeling and lung inflammation. Understanding CHF-induced lung remodeling is also critical to understand the right ventricular failure. However, this area is largely unstudied. Regulating CHF-induced lung remodeling and the underlying... 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

To deal end-stage CHF will need team efforts from heart, lung, blood and immunology.

Name of idea submitter and other team members who worked on this idea Yingjie Chen, Associate Professor, University of Minnesota

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13 net votes
15 up votes
2 down votes
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Goal 2: Reduce Human Disease

Cure COPD

How can the structure and function lost in COPD be restored?

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 tissue alterations in COPD and their physiologic consequences of those changes are reasonable well described. It is now clear that, like all organs, the lung can repair damaged tissue and that repair processed can be modulated. Strategies for assessing restoration of lost tissue structure and function should be developed, together with the development of clinical measures that can gauge progress of treatment.

Feasibility and challenges of addressing this CQ or CC

Animal studies demonstrate that emphysema can be repaired, at least in some species. Several forms of airways disease in humans are also reversible. Studies of interventions to augment tissue repair are needed with the goal of applying them to clinical interventions.

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

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18 net votes
20 up votes
2 down votes
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Goal 1: Promote Human Health

Circadian-coupled rhythms in lung health

Does the homeostasis and health of the lung depend on circadian-coupled genomic function?

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

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The circadian genome is a highly conserved system producing 24-hr rhythms in gene expression in the lung. Uncovering the molecular/cellular pathways under circadian control and their significance would provide a new generation of mechanistic understanding of lung health and development.

Feasibility and challenges of addressing this CQ or CC

Delineating circadian mechanisms of lung function would enable new strategies to phenotype, diagnose, and mange lung disease to be developed and tested.
Over the past decade, new discovery has uncovered a mechanistic interface between the circadian clock and fundamental cellular processes including oxidative stress, cell metabolism, immune and inflammatory responses, epigenetic modification, hypoxia/hyperoxia response pathways, endoplasmic reticular stress, autophagy, and regulation of the stem cell environment. While each of these processes is involved in lung function, the significance of circadian regulation in the development and maintenance of lung health is not well-understood.

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

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11 net votes
25 up votes
14 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?

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 »

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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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?

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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