Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

The Importance of the Microbiome in Recovery after Hematopoietic Stem Cell Transplantation

Do modifications in the recipient gut or lung microbiome affect development of tolerance and immunologic recovery after allogeneic hematopoietic stem cell transplantation (HCT) and can re-institution of a more normal microbiome lead to improved outcomes?

Submitted by (@marymh)

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

Details on the impact of addressing this CQ or CC :

HCT leads to profound changes in the host microbiome. Some small studies indicate that differential recovery of the gut microbiome is associated with differential outcomes, including graft-versus-host disease and mortality. Less is known about the pulmonary microbiome. Better understanding of the role of the microbiome in facilitating posttransplant recovery could lead to easily administered interventions and provide important insights into the role of different subpopulations of the microbiome on the health of all people.

Feasibility and challenges of addressing this CQ or CC :

Preclinical and clinical studies of this area would be greatly facilitated by a microbiome repository linked to high quality clinical data and would provide opportunity for insight into the role of the microbiome in health and disease.

Name of idea submitter and other team members who worked on this idea : Mary Horowitz

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Goal 2: Reduce Human Disease

Studying Gender Differences

Considering the dearth of research on gender differences, NHLBI should expand the portfolio of opportunities available for studies in this area.

Submitted by (@golan0)

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

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Goal 2: Reduce Human Disease

What do we know about Heart Failure with Preserved Ejection Fraction (HFpEF)

Mortality is similar between HFpEF and HFrEF but we have currently no viable therapeutic option for HFpEF. There have been many large trials, but they all failed. Our basic understanding of the disease is very limited which contributed to failures of many prior trials and wasting $$$. We know very little about the pathophysiology of the disease . It is time to get back to the basic science and use our new tools (e.g. ...more »

Submitted by (@rezanezafat)

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

Details on the impact of addressing this CQ or CC :

Better therapy for HFpEF is an unmet clinical needs which will impact millions of patients

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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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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?

Submitted by (@kathi0)

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

Implanted defibrillators

What are the effects of implanted defibrillators (ICDs) in patients with diseased, remodeled hearts?

Do ICDs influence future arrhythmia risk? Can devices be better designed to mitigate their possible deleterious effects?

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 :

Decrease cardiovascular disease and death. Improve quality of life for those utilizing ICDs.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in research and ICD technology

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

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Goal 2: Reduce Human Disease

Novel methods to diagnose and treat microvascular ischemia

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

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 :

Development of effective diagnostics would lead to improved treatments for myocardial and non-myocardial microvascular ischemia, and also advance understanding to extend the advance beyond this setting.

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

Sarcoidosis Awareness

I don't understand why that with so many people suffering and there is still no cause or cure. This disease isn't a new disease and it is still having trouble getting recognized by The Government who make the very ill work instead of giving them the disability they deserve. I understand that Cancer is a horrible disease, but having Sarcoidosis can be just as bad as a sentence as having cancer. Live one day in my body. ...more »

Submitted by (@fjr311)

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

Details on the impact of addressing this CQ or CC :

We are a non profit organization that is trying to raise money for Sarcoidosis Patients who can't afford their medicines and other financial obligations, due to many can't work because the disease takes their body away from them and limits them.

Sarcoidosis (pronounced SAR-COY-DOE-SIS) is an inflammatory disease that can affect almost any organ in the body. It causes heightened immunity, which means that a person’s immune system, which normally protects the body from infection and disease, overreacts, resulting in damage to the body’s own tissues. The classic feature of sarcoidosis is the formation of granulomas, microscopic clumps of inflammatory cells that group together (and look like granules, hence the name). When too man y of these clumps form in an organ they can interfere with how that organ functions.

In people of the United States, sarcoidosis most commonly targets the lungs and lymph nodes, but the disease can and usually does affect others organs, too, including (but not limited to) the skin, eyes, liver, salivary glands, sinuses, kidneys, heart, the muscles and bones, and the brain and nervous system.Locally, nationally and internationally, Sarcoidosis of Long Island is a charitable organization to provide emotional,and financial assistance to individuals living with Sarcoidosis as well as partnering with other organizations to help find a cure. There are many people with Sarcoidosis that can't get disability because it is not recognized as a disability.

Feasibility and challenges of addressing this CQ or CC :

I just want to let everyone know that no matter how hard it has affected my life, I will keep a smile on my face. Even though I am on disability, I know that it may have changed my life but it won’t run my life. I refuse to give into this disease, don’t get me wrong there are days where I cry and ask why me.I just answer myself by saying God only gives you what you can handle. I use a cane now and then but that doesn’t define me. What defines me is the strength to carry on. Sarcoidosis is what I have not what I am! My mission in life is to help others with diseases that on the outside you look fine, but on the inside the pain is unbearable.In December of 2013 I ended up having another surgery to fix the mesh of the hernia so that makes a total of 6 surgeries in 3 years. But I am still here kicking and fighting.

My Sarcoidosis thoughts as I live and move forward with this disease.

I know that I am not perfect and will never be, but I do know one thing. I would do as much as I could to help others anyway legal. I am not trying to put myself on a pedestal, but us as a "Sarkie" nation, which many of us do, need to get together and get this whole movement working together. We are all in it for the right reasons, now let's keep the momentum going so we can all get this disease controlled and then see it go to the waste side.Good news is in April Sarcoidosis of Long Island is going to be working with The Town of Brookhaven for a walk through Beautiful and Historic Stony Brook.

Name of idea submitter and other team members who worked on this idea : Frank Rivera- Sarcoidosis of Long Island

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Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease - Contribution of Airways Disease

What is the contribution of airways disease to acute and chronic pulmonary distress?

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 :

What is known about this topic:

 

1) Pulmonary function testing is abnormal in 80-90% of kids and 90% of adults with SCD.

 

2) SCD kids with asthma have a higher frequency of ACS and those with a history of ACS have a higher prevalence of asthma.

 

3) An elevated TRV in SCD kids and adolescents may not predict mortality but does predict reduced exercise capacity at 22 months which may be irrespective of pulmonary hypertension

 

4) Dyspnea is extremely common in adults with SCD; 50% of HbSS and 40% of HbSC adults report at least mild dyspnea on exertion. The mechanisms responsible for this are unknown.

 

5) Bronchodilators are often used to treat patients with ACS, yet their benefit is unclear.

 

6) Systemic steroids will increase the rate of rebound pain if used during a vasoocclusive crisis.

 

7) Asthma in SCD is frequently under-treated because of fears associated with systemic and even inhaled corticosteroid use.

Feasibility and challenges of addressing this CQ or CC :

Areas of Controversy:

1) Is there an inter-relationship between airway and vascular disease in SCD?

 

2) Are systemic corticosteroids safe in SCD? Are they indicated in treatment of ACS? Are they indicated for treatment of asthma exacerbations?

 

3) Are inhaled corticosteroids useful in treating or preventing ACS?

 

4) What are the mechanisms responsible for the decline in exercise capacity observed as SCD patients go from late adolescence to early adulthood?

 

5) Will more aggressive treatment of asthma prevent this decline?

 

6) What role does nocturnal hypoxemia and OSA play in disease modulation of SCD?

 

7) What are the mechanisms of the restrictive physiology observed by PFTs primarily in adults?

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

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Goal 2: Reduce Human Disease

What about the impact of regulation of genes in response to external stimulation on human health

We are focusing a lot on the genes that may be protective or harmful to our lives. But what about the regulation of genes in response to external stimulations, such as psychosocial and/or environmental, that are probably more accountable for whether we live healthier or not.

Submitted by (@jiang001)

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

Details on the impact of addressing this CQ or CC :

Rationale: Years of research in the mind-heart field have set examples that looking at changes during dynamic stimulations (chronic, acute, and acute superimposed on chronic) are more meaningful for us to better understand how the body truly works. Therefore, research design in mimicking real dynamic process is necessary to truly capture the healthy or harmful phenotypes driven by genotypes. I suggest the NHLBI to establish a platform gathering resources to promote more sophisticated research from basic to clinical to better understand the underlying mechanisms of psychosocial impact on cardiovascular diseases that has come to a sizable problem for the human being in US and world wide.

Feasibility and challenges of addressing this CQ or CC :

We have performed researches that allow us to identify phenotypes that are only appearing under emotional stress testing. Currently we are examining whether certain intervention may modify these kinds of changes. Even our studies fail to demonstrate changes with intervention, the findings support future studies focusing on testing dynamic changes under stress that reflects daily living. Resting data obtained in laboratory does not truly represent what human beings experiences.

Name of idea submitter and other team members who worked on this idea : Wei Jiang from Duke University

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Goal 2: Reduce Human Disease

Targeting Preclinical Diastolic Dysfunction to Prevent Heart Failure

Heart failure (HF) affects over 5 million American adults, and projected estimates show growth of this epidemic by 25% over the next 15 years as the population of the United States continues to age. Heart failure with preserved EF (HFpEF) encompasses 50% of all heart failure cases. Preclinical diastolic dysfunction (PDD) is defined as normal systolic function, moderate or severe diastolic dysfunction determined by Doppler ...more »

Submitted by (@chen.horng)

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

Details on the impact of addressing this CQ or CC :

There is currently no FDA approved therapy for HFpEF and yet HFpEF makes up 50% of all HF population. The prevalence of PDD (ACC/AHA Stage B HF) is abt 28% of the general population and these patients do not have symptoms of HF. Understanding the pathophysiology of PDD may leady to the development of therapeutic strategies to prevent the development of HFpEF. This would decrease the burden of HF impact public health and be cost-effective, similar to the use of vaccine to prevent infectious diseases.

Feasibility and challenges of addressing this CQ or CC :

With echocardiography, we are able to identify PDD patients before they develop symptomatic HF. Hence with research funding, we can better characterize preclinical diastolic dysfunction, and to discover further targets for this entity to prevent development of HFpEF

Name of idea submitter and other team members who worked on this idea : Horng H Chen

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Goal 2: Reduce Human Disease

RCT of stepped-care depression treatment on CV events & death

Does treating depression improve survival and reduce major adverse cardiac events in acute coronary syndrome patients?

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 :

A substantial evidence base now exists showing that depression is associated with a two-fold increased risk of death and recurrent CV events in cardiac patients, leading to a recent AHA scientific statement recommending its elevation to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014). Yet there is currently no clinical trial evidence that reducing depression improves cardiac morbidity and mortality. A clinical trial, using new, more effective depression treatment methods, such as collaborative care approaches that combine psychological counseling with medication in stepped-care fashion, is needed to determine whether effective treatment of depression can improve survival and reduce clinical cardiovascular events in cardiac patients.

Feasibility and challenges of addressing this CQ or CC :

Newer stepped-care treatments for depression, combining medication and psychotherapy, have recently been developed and found to more effectively reduce depression than earlier treatments. By using these newer treatment methods to substantially lower depression, we can better answer the question as to whether treating the newly acknowledged risk factor of depression in ACS patients can improve clinical outcomes in these patients.

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

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