Goal 3: Advance Translational Research

Adaptive trial design for clinical research

Will adaptive trial design improve clinical research for acute lung injury?

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 : American Thoracic Society member

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Goal 2: Reduce Human Disease

Genomic signature in animal models

What is the genomic signature in a relevant animal model with translational significance for human pulmonary disease?

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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-7 net votes
6 up votes
13 down votes
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Goal 1: Promote Human Health

Enhancing Understanding of Determinants of Health in Rural Areas & Developing Solutions

What are the biological, environmental, social and economic determinants of health in rural areas related to COPD and other lung disease.

Submitted by (@gacdk0)

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

Details on the impact of addressing this CQ or CC :

There are extreme disparities in the impact of COPD in rural areas, especially in rural Appalachia. These areas experience much larger prevalence rates and higher rates of hospitalization, readmissions and other health indicators that contribute to increased cost and decreased quality of life. These are also areas with the least ability to make improvements. Research that can inform both the causes of these disparities and identify proven methods for systematically confronting these issues has the potential to dramatically improve overall health status in rural America

Name of idea submitter and other team members who worked on this idea : Grace Anne Dorney Koppel

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7 net votes
8 up votes
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Goal 2: Reduce Human Disease

Improve Repair of injured lung

Why can’t we improve outcomes following acute lung injury. A half century of ICU interventions have resulted in only incremental improvements in survival and morbidity following acute lung injury. While we have pursued innumerable strategies for decreasing ventilator associated exacerbation of lung injury, we have failed to identify treatable common or selective pathways from the initial injury that can be targeted post ...more »

Submitted by (@dcenter)

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

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5 net votes
8 up votes
3 down votes
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Goal 2: Reduce Human Disease

Lung Transplantation

Although the majority of lung recipients experience significant health improvement, they also frequently face serious symptom distress, impaired physical functioning and poor quality of life due to post-transplant morbidity, such as chronic rejection, infection and multiple side-effects of immunosuppression. a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management ...more »

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 :

a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management behaviors so that patients and clinicians working together can achieve optimal control of disease, reduce symptom distress and complications, and promote quality of life.

 

b) Evaluate the impact of integrating palliative care and transplant care for symptom management, goal setting and advanced care planning along the entire lung transplant illness trajectory (pre, post and end of life).

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

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Goal 2: Reduce Human Disease

Therapy for lung infections

1. Monotherapy with a quinolone vs combination therapy with a 3rd generation cephalosporin. The issue of the best antibiotic treatment for severe CAP has been a major area of contention now for a decade and it is the most common cause of infectious death in the United States. 2. Combination therapy vs monotherapy for pneumonia due to Pseudomonas. This is another major area of contention – for nearly 2 decades, and generates ...more »

Submitted by (@nhlbiforumadministrator)

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

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

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Goal 2: Reduce Human Disease

Can transcutaneous carboxyhemoglobin measure endogenous heme oxygenase activity?

Non-invasive measurement of transcutaneous carboxyhemoglobin (SpCO) by CO-oximetry has been shown to reflect disease activity in asthma, allergic rhinitis, Staphylococcal pneumonia/sepsis and to correlate positively with lung function in cystic fibrosis. Given published studies of heme oxygenase activity in these diseases as a reflection of oxidant or inflammatory activity, does measurement of SpCO reflect endogenous ...more »

Submitted by (@lekurlandsky)

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

Details on the impact of addressing this CQ or CC :

Laboratory measurement of heme oxygenase activity in inflammatory and states of oxidative activity in multiple disease states, lung diseases for instance, has become important in measuring disease severity and activity as well as being an indicator of disease modification by gene polymorphisms of heme oxygenase. The simple measurement of transcutaneous carboxyhemoglobin if correlated with heme oxygenase activity would provide a ready assessment for clinicians in the clinical setting.

Feasibility and challenges of addressing this CQ or CC :

In a setting in which heme oxygenase activity is measured and clinical patients of varying diseases are available, this question could be answered reasonably easily without technical difficulty.

Name of idea submitter and other team members who worked on this idea : Lawrence E. Kurlandsky, MD

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Goal 2: Reduce Human Disease

Prenatal effects on pulmonary disease

What are the prenatal determinants of adult pulmonary disease?

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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-2 net votes
14 up votes
16 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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102 up votes
22 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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15 up votes
10 down votes
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Goal 1: Promote Human Health

Stem cell niche in the lung

How do lung progenitors recognize stem cell niches, and what cell-cell interactions mediate normal repair?

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 :

Research on the stem cell-niche interaction will enhance our understanding of stem cell behavior, enable manipulation of stem cell activity and differentiation potential, and facilitate the development of stem cell-based therapy.

Feasibility and challenges of addressing this CQ or CC :

Developing novel models for in vitro 3D culture and in vivo transplantation assays will facilitate the progress.

 

Recent advances have identified and characterized several lung progenitor cell types. However research gaps remain on understanding the interaction of stem cells with the niche, and how the microenvironment impacts on the stem cell activity during injury/repair.

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

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23 up votes
15 down votes
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Goal 2: Reduce Human Disease

Harnessing Lung Regenerative Capacity to Improve and Increase Donor Lungs for Transplantation.

Using knowledge of matrix biology and lung development, what are useable methods to modify cadaveric donor lungs to provide a durable, effective organ replacement therapy?

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 :

A major advance in this area will increase the number of donor lungs available for lung transplantation

Feasibility and challenges of addressing this CQ or CC :

A number of stem and progenitor cells involved in lung repair and regeneration have been identified. Targeting them for expansions in damaged donor lungs may turn these damaged lungs into healthier lungs that can then be used for lung transplant safely.

Most of the donor lungs are not suitable for lung transplantation because the premorbid conditions of the donors often also damaged the lungs. Bioreactors have been used to “rehab” these damaged lungs and optimizing the ex vivo condition in these bioreactors may accelerate the lung repair process.

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

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18 up votes
17 down votes
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