Goal 2: Reduce Human Disease

Interstitial Lung Disease

Do the non-pharmacological interventions of pulmonary rehabilitation and supplemental oxygen for exertional hypoxemia improve quality of life and functional status in patients with chronic fibrotic ILD?

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 :

There is good evidence from small controlled trials that pulmonary rehabilitation improves walk distance and shortness of breath in patients with chronic ILD. Both pulmonary rehabilitation and supplemental oxygen are commonly recommended to these patients at great cost. A randomized clinical trial using factorial design could address the impact of these two therapies individually as well as together on clinically meaningful outcomes.

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

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Goal 2: Reduce Human Disease

Fibrosis Care Center Network and Patient Registry

Complex diseases such as interstitial lung disease and pulmonary fibrosis requires a collaborative effort to effectively characterize, appropriately diagnose, and efficient evaluate novel therapies. Similarly, basic, translational and clinical research in this field requires the integration of clinical phenotypes with biologic specimens. We propose the expanded development of the Care Center Network and Patient Registry ...more »

Submitted by (@gcosgrove)

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 envisioned impact of an integrated Care Center Network and Patient Registry is to create a resource that:

 

• Informs the understanding of interstitial lung disease (ILD), its epidemiology and natural history;

• Assists to understand treatment patterns associated with optimal outcomes that will inform an emerging standard of care and development of treatment guidelines;

• Facilitates patient and clinician engagement in support of future prospective studies;

• Furthers study of biomarkers and predictors of disease and severity;

• Documents patient experience of living with ILD as described through patient reported outcomes (PRO) including quality of life, functioning, and symptoms;

• Generates new hypotheses and new endpoints in support of future studies;

• Increases awareness of relevant issues and needs among the immediate ILD community;

• Provides the opportunity to promote and inform policies in the larger health care community in support of those with ILD

Feasibility and challenges of addressing this CQ or CC :

With the establishment of collaborations between several partners, we initiated the PFF Care Center Network and Patient Registry in 2014. The Care Center Network and Patient Registry has since expanded to 21 centers regionally dispersed throughout the United States. The challenges of effectively and efficiently investigating the cause, care and treatment of pulmonary fibrosis are predominantly those of organization and integration of effort. Expertise is present throughout the United States. We suggest that with the continued expansion of the Care Center Network and Patient Registry, those challenges will be overcome and the focus of the fibrosis community efforts can be on diligently investigating the diseases that devastatingly affect patients. An integrated repository of well-phenotyped patients and biologic specimens is the first step in Precision Medicine for patients with interstitial lung disease and pulmonary fibrosis.

Name of idea submitter and other team members who worked on this idea : Gregory P. Cosgrove, MD, The Pulmonary Fibrosis Foundation

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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?

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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Goal 2: Reduce Human Disease

Persistent Burden of HIV Infection on Lung Health in the U.S. and Globally

Despite the advent of HAART the lung and vascular compartment continue to bear the brunt of complications associated with HIV infection. Potential causes include the establishment of HIV latency in the lung, inability of current therapeutic agents to treat latent reservoirs, inadequate immune reconstitution in the lung, and persistent impairment of normal lung homeostasis after treatment (i.e. persistent alterations ...more »

Submitted by (@htwig0)

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

Details on the impact of addressing this CQ or CC :

Lung disease remains a major contributor to HIV morbidity in the HAART era. In fact, the lung continues to bear the burden of chronic HIV complications. The cause of this is likely multifactorial, including:

 

1. Persistence of HIV reservoirs. The lung is populated by long lived cells which makes them uniquely situated to serving as reservoirs. A better understanding of viral latency in the lung is needed.

 

2. Inadequate immune reconstitution. This can lead to persistent increased risk to chronic infections and poor tumor surveillance. It is well recognized that earlier initiation of antiretroviral therapy, rather than waiting till immune exhaustion, leads to better immune reconstitution. Thus to improve lung immune reconstitution will need better approaches to diagnosing HIV early. Furthermore, studies are needed to better define when adequate lung immune reconstitution has occurred.

 

3. Persistent abnormalities in normal lung homeostasis. Despite the absence of detectable replicating HIV in the lung there appears to be persistent alterations in the lung inflammatory state. Abnormalities in the lung microbiome and virome could also remain. Lastly, risk factors that may have contributed to HIV infection and lung disease in the first place (i.e. smoking, IVDU) persist in patients on therapy. Contributions of these risk factors towards lung disease in the HIV-infected population are sorely needed.

Feasibility and challenges of addressing this CQ or CC :

Given the continued large burden of the HIV population in the U.S. and globally these studies are certainly feasible. One of the biggest challenges will be the identification of an appropriate control nonHIV-infected cohort that shares the same risk factors (i.e. smoking, IVDU) as the HIV-infected population. Historically this has been problematic given the known demographic differences in the HIV population (i.e. increased prevalence of smoking, greater male to female ratio, differences in other HIV risk factors). The second major challenge is the recognition that the new spectrum of lung complications in HIV-infection are chronic in nature and thus will require long term longitudinal studies to adequately assess the critical questions raised here. Finally, it must be recognized that the greatest burden of HIV infection lies outside our borders in third world countries. In addition to the high prevalence of HIV infection in these regions, the major infections complications, which have been largely controlled in the U.S. through early antiretroviral therapy, continue to play a major role in HIV morbidity and mortality. Thus one cannot forget that first and foremost untreated HIV infection leads to profound immunosuppression with an associated increased risk of usual and opportunistic infections.

Name of idea submitter and other team members who worked on this idea : Homer L. Twigg III on behalf of the INHALD Consortium

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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

Pulmonary Vascular Diseases

Does pulmonary rehabilitation or regular exercise improve outcomes in patients with PVD?

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 :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

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

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Goal 2: Reduce Human Disease

Nontuberculous mycobacterial (NTM) lung infections

The true prevalence of Nontuberculous mycobacterial (NTM) lung infections remains incompletely understood, however several aspects of NTM lung disease prevalence are becoming more clear. NTM lung disease is currently more common in the U.S. than TB (by a factor of 3) and has consistently been shown to be increasing in prevalence. When viewed in the context of likely universal environmental NTM exposure this increasing ...more »

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 :

NTM lung disease is most common among older and female patients with estimated prevalences as high as 50-60 cases per 100,000 in this group and can be seen in this context as a women’s health issue.  While it may appear paradoxical, NTM lung disease studies would both profoundly change outcomes for a relatively rare condition overall, but would also benefit, in a potentially profound way, a large number of patients in a selected population (older female patients) in which the disease is not so rare.   To date there has been no significant funding for any aspect of NTM lung disease outside of limited support from the pharmaceutical industry.  The studies that have been done to date are largely single center/institution studies with relatively small numbers of patients.  Again, the few collaborative studies that have been done were accomplished with support from the pharmaceutical industry.  NTM lung diseases, and associated lung diseases such as bronchiectasis have not attracted the interest or support of major non-industry funding sources.

Feasibility and challenges of addressing this CQ or CC :

Essentially every aspect of Nontuberculous Mycobacterial (NTM) lung disease is associated with some level of controversy. The diagnostic guidelines were adopted primarily as a result of experience with common NTM pathogens such as Mycobacterium avium complex (MAC), M. kansasii , and M. abscessus. The relevance of the diagnostic guidelines for other potential NTM pathogens, especially rarely encountered organisms (in the U.S.) such as M. xenopi and organisms usually associated with specimen contamination such as M. fortuitum , is untested and unknown. The treatment of NTM lung disease is almost entirely based on case series, both retrospective and prospective, with consensus on basic treatment concepts. Treatment outcomes remain unsatisfactory for many pathogens including the most common, MAC, and prospective treatment trials are needed to establish not just optimal treatment regimens but the roles of agents in common use, such as clofazimine, the fluoroquinolones and inhaled amikacin, of unproven value.  Other basic studies including radiographic and pulmonary function evolution for treated and untreated disease and long term natural history of treated and untreated NTM lung disease patients are lacking.

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

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 »

Submitted by (@chenx106)

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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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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Goal 2: Reduce Human Disease

Cure COPD

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

Submitted by (@jsullivan)

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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