Showing 5 ideas for tag "cardiopulmonary"

Goal 2: Reduce Human Disease

Inflammation and outcomes following pediatric cardiac operations

What is the contribution of the inflammatory response to postoperative recovery following pediatric cardiac operations and what strategies can improve outcomes?

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

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Congenital heart disease is the most common cause of birth defects, with about 40,000 new cases born per year in the US. Affected individuals experience morbidity and mortality that generate health and economic consequences significantly out of proportion to their numbers. An estimated 10,000 of these patients will undergo cardiac surgery involving cardiopulmonary bypass (CPB). Furthermore, it is estimated that over 300,000 children in the US under age 21 have congenital cardiovascular disease and that 38% of these children will have had one or more surgical procedures. The use of CPB in neonates in particular has increased steadily over the past two decades. Further, neonates are generally sicker and consume more resources, including postoperative mechanical ventilation, ICU stay and hospital stay. Consequently, reducing the deleterious effects of CPB will have the largest impact in this group of patients.

Feasibility and challenges of addressing this CQ or CC

Research has begun to assess the inflammatory response to cardiopulmonary bypass in pediatrics. However, the magnitude and importance of its contribution to complicating postoperative recovery remains elusive. Clinical trials have begun to assess the efficacy of generalized anti-inflammatory therapies, typically steroids, with conflicting results. No therapy has been recognized as the standard of care. It’s critical that we improve our understanding of the molecular and cellular mechanisms of this inflammatory response and resulting derangements in vascular permeability and develop novel treatment strategies for infants and children undergoing cardiopulmonary bypass.

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Goal 2: Reduce Human Disease

Mechanism of Cardiopulmonary dysfunction in Duchenne

What is the exact mechanism affecting the cardiopulmonary cascade of events that occurs in Duchenne?

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

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Very little is truly known about the cardiopulmonary cascade in Duchenne. While patients are tested (pulmonary function testing, sleep studies) and encouraged to use assistive devices (cough assist, non –invasive and invasive assisted ventilation), we have no insight into exactly what is happening to the diaphragm, accessory muscles, effects on the heart, etc. that results in sudden death. The investigation of this area is vital to the well being of this patient population, and represents a gap in both research and care.

Feasibility and challenges of addressing this CQ or CC

identifying the exact mechanisms of the cardiopulmonary decline in Duchenne would allow the development and implementation of appropriate interventions, delaying, and possibly, preventing this cascade of events that lead to sudden death in this disease. The implications for Duchenne are tremendous. Likewise, the implications for other muscular dystrophies resulting in cardiopulmonary deaths, as well as other diagnoses resulting in cardiomyopathy, cardiac and pulmonary failure, would benefit as well.

Name of idea submitter and other team members who worked on this idea Parent Project Muscular Dystrophy

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Goal 2: Reduce Human Disease

Functional pulmonary imaging with noninvasive imaging techniques

Critical Challenge

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

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Pulmonary dynamics are altered with diffuse lung disease. Pulmonary function testing is a mainstay for evaluating patients with diffuse lung disease. However, ability to assess alterations of local lung mechanics and physiology may elucidate those patients with varying outcomes and mechanisms of disease. Such local analysis is possible with imaging such as MR and quantitative computed tomography (CT).

Feasibility and challenges of addressing this CQ or CC

Dynamic magnetic resonance imaging (MR) techniques are available that are capable of evaluating the oxygen delivery and blood flow to regional areas of the lung and measurement of pressures in the heart and vasculature. Additionally, advanced dual-energy CT techniques enable assessment of blood volume within the lungs. Such techniques can be applied to pulmonary vascular and pulmonary parenchymal disease and combinations of the two. For example, an understanding of the cardiopulmonary interaction and phenotyping of pulmonary hypertension is needed. A need exists to determine if advanced CT technology and MR can identify patients with the emerging phenotypes of combined pulmonary hypertension, in which the degree of pulmonary hypertension is greater than expected from cardiac and pulmonary causes. MR can potentially serve as early predictors of these phenotypes, given MR’s ability to evaluate the parenchyma, the pulmonary vasculature, and heart, and in combination with other biomarkers determine appropriate therapy.

Name of idea submitter and other team members who worked on this idea Society of Thoracic Radiology

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Goal 2: Reduce Human Disease

Correlation of genetic modifiers and cardiopulmonary fibrosis/dysfunction in Duchenne

What are the protective genetic modifiers that may be associated with a Duchenne phenotype more resistant to the development of cardiac and pulmonary fibrosis and subsequent pulmonary/cardiac dysfunction? . Are there genetic modifiers that may ameliorate or enhance the onset of cardiac and/or pulmonary dysfunction?

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 two major causes of death in Duchenne are cardiac and pulmonary dysfunction. The onset of cardiac and pulmonary dysfunction in people living with Duchenne follows a heterogeneous path, not necessarily consistent with the underlying genotype or onset musculoskeletal dysfunction. This can often be seen in siblings/relatives with identical genetic mutations and very different disease progression.

Feasibility and challenges of addressing this CQ or CC

A number of studies have provided some degree of evidence for the presence of genetic modifiers in Duchenne, which may affect disease onset and musculoskeletal progression. Two of these modifiers, LTBP4 and SPP1 have been shown to have a profound effect on time to loss of ambulation, establishing the need for and feasibility of identification of genetic variants that impact the cardiorespiratory phenotype in Duchenne.
Several reports have alluded to the impact of genetic modifiers on pulmonary and/or cardiac disease progression in animal models. Further studies validating the presence and impact of these modifiers may have implications for the prevention, or postponement, of cardiac and pulmonary dysfunction in Duchenne, as well as other, muscular dystrophies, allowing enhancement of both quantity and quality of life.
In addition, drug development with pulmonary and/or cardiac primary or secondary outcomes, may be impacted by populations with genetic mutations that include genetic modifiers. At least one of the already identified genetic variants affects skeletal muscle responsiveness to corticosteroid treatment. The validation of the presence, and impact, of these modifiers, may impact the outcomes of these trials, and help delineate populations most likely to benefit from these new therapies.

Name of idea submitter and other team members who worked on this idea Parent Project Muscular Dystrophy

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Goal 2: Reduce Human Disease

Correlation between abdominal/diaphragmatic fibrosis and cardiopulmonary dysfunction in Duchenne

Is there a correlation between the development of abdominal/diaphragmatic fibrosis and the development of cardio-pulmonary dysfunction? Are there mechanisms (i.e., pulmonary excursion therapy) that may prevent/postpone the development of diaphragmatic fibrosis and subsequent pulmonary dysfunction?

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

Details on the impact of addressing this CQ or CC

currently there is no adequate method of evaluating the development of fibrosis in the diaphragm. Mdx mouse models have provided insight into this progression, and to a possible correlation between abdominal fibrosis and cardiac dysfunction.

Feasibility and challenges of addressing this CQ or CC

: Maintaining cardiopulmonary function in Duchenne has been the mainstay of therapy, however little attention has been given to the accessory muscles of respiration. Supporting the muscles of respiration may prevent or postpone the ongoing process or cardiopulmonary dysfunction, resulting in an increased the lifespan, and quality of life, of people living with Duchenne. The current base of researchers addressing the cardiopulmonary issues in Duchenne, as well as the resources to identify and track patients with cardiopulmonary dysfunction, enhances the feasibility of answering this question.

Name of idea submitter and other team members who worked on this idea Parent Projct Muscular Dystrophy

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