Goal 3: Advance Translational Research

Identifying Biomarkers of Chronic Lung Diseases

What are the biomarkers that identify expression and progression of specific subtypes of chronic lung disease?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Most chronic lung diseases, including COPD, do not have biomarkers that reflect disease pathogenesis accurately. Readily measurable biomarkers, especially in peripheral blood, would be key tools for clinical trials and studies of disease heterogeneity.

Feasibility and challenges of addressing this CQ or CC :

The most useful chronic lung disease biomarkers would be proteins, metabolites, or gene expression measurements in peripheral blood. Defining useful peripheral blood biomarkers that reflect lung disease pathogenesis will require validation that the lung disease process can be captured in peripheral blood measurements.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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42 net votes
62 up votes
20 down votes
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Goal 3: Advance Translational Research

Applying Imaging in Chronic Lung Diseases

How can chest CT or other imaging tools be optimally used to characterize expression and progression of chronic lung disease?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chest CT scans provide anatomical information on disease pattern and severity that cannot be readily obtained otherwise. These imaging studies could be essential in reclassifying chronic lung diseases more effectively and in assessing disease progression more accurately.

Feasibility and challenges of addressing this CQ or CC :

The increasing use of chest CT scans for lung cancer screening will provide a large number of imaging studies that could transform pulmonary research in multiple chronic lung diseases. However, the images will need to be appropriately collected and analyzed.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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33 net votes
47 up votes
14 down votes
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Goal 2: Reduce Human Disease

Understanding COPD Manifestations in Subjects without Overt Airflow Obstruction

What is the pathogenesis and appropriate treatment for subjects with chronic respiratory symptoms or imaging abnormalities who do not have overt airflow obstruction (and thus are not currently categorized as having COPD)?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

COPD is currently diagnosed by spirometry, but many other individuals (primarily smokers) have respiratory symptoms and/or imaging abnormalities that suggest lung damage. Identifying subjects with pre-obstruction manifestations of COPD could lead to more effective treatment and prevention.

Feasibility and challenges of addressing this CQ or CC :

COPD subjects often develop ongoing inflammation that persists long after smoking cessation. It is unknown when this cycle of inflammation begins or what causes it.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and the COPDGene Executive Committee

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32 net votes
47 up votes
15 down votes
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Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Goal 2: Reduce Human Disease

Diagnosis and Treatment of the Asthma-COPD Overlap Syndrome

Asthma-COPD overlap syndrome is common and associated with increased morbidity and greater healthcare costs. However, ACOS patients are usually excluded from studies of either disease. There is a compelling need for research in order to define objective diagnostic criteria for ACOS.

Submitted by (@craighersh)

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 diagnostic criteria as well as biomarkers will allow for efficient targeting of specific therapies for ACOS, such as biologic therapies developed for asthma.

Feasibility and challenges of addressing this CQ or CC :

Since ACOS subjects are usually excluded from COPD or asthma trials, this will require identification of study populations that did not exclude ACOS and/or enrollment of ACOS subjects into a new study.

Name of idea submitter and other team members who worked on this idea : C. Hersh

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30 net votes
31 up votes
1 down votes
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Goal 3: Advance Translational Research

Integration of Multiple Omics Data in Chronic Lung Diseases

Integration of multiple Omics data types (genetics, transcriptomics, metabolomics, proteomics, and epigenetics) to understand susceptibility, progression, and heterogeneity of chronic lung diseases.

Submitted by (@jdc000)

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 single Omics data type is likely to adequately describe the pathogenesis and heterogeneity of chronic lung diseases including COPD, asthma, and IPF. However, integration of these data types using systems biology and network approaches could transform the diagnosis, prognosis, and treatment of these chronic lung diseases.

Feasibility and challenges of addressing this CQ or CC :

The availability of multiple Omics data at fairly reasonable costs provides unique opportunities for multiple Omics research.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and the COPDGene Executive Committee

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26 net votes
45 up votes
19 down votes
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Goal 3: Advance Translational Research

What is the comparative effectiveness of short-term vs. chronic (e.g., 12 mo) pulmonary rehabilitation?

What is the comparative effectiveness of short-term vs. chronic (e.g. 12 mos) pulmonary rehabilitation on survival, patient-reported outcomes (symptom frequency, activities of daily living, quality of life, sleep quality, exacerbations), healthcare utilization, and costs from a societal and healthcare system perspective?

Submitted by (@jakris)

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

Details on the impact of addressing this CQ or CC :

Modest sized efficacy trials demonstrate substantial health benefits, that wane as Pulmonary rehabilitation is discontinued. We need to test the health and resource implications of "chronic" (e.g., 12 or 24 mos) pulmonary rehabilitation. Such information will benefit health systems seeking to implement care models for high-risk, costly, patients - patients with COPD are of increasing interest to health systems. Such a comparative effectiveness trial should also involve behavioral interventions to promote self-management and involve caregivers.

Name of idea submitter and other team members who worked on this idea : Jerry Krishnan

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26 net votes
32 up votes
6 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 »

Submitted by (@jimandmarynelson)

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

Details on the impact of addressing this CQ or CC :

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

Early COPD

What does early COPD actually look like. This is defined as severe COPD 30 years prior to its manifestation.

Submitted by (@davidmannino)

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

Details on the impact of addressing this CQ or CC :

Prevention programs in COPD either target smoking or those with established disease. Better understanding the factors that lead to the development of COPD (both in ever and never smokers) is critical to improved disease prevention.

Feasibility and challenges of addressing this CQ or CC :

We need to revisit long term studies in novel ways- and look at new cohorts. Better biomarkers need to be developed.

Name of idea submitter and other team members who worked on this idea : Dave Mannino

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22 net votes
31 up votes
9 down votes
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Goal 3: Advance Translational Research

Do Alpha-1 Antitrypsin Deficiency and Cystic Fibrosis Inform COPD? Have we been looking?

Cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (AATD) share phenotypic features with common COPD including airflow obstruction and airway mucociliary dysfunction. Although research in CF and AATD has advanced our understanding of those rare diseases, it has yet to explain common COPD. Do Alpha-1 Antitrypsin Deficiency and Cystic Fibrosis Inform COPD? Could therapies currently in use or under development for ...more »

Submitted by (@kerickson)

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 mechanisms leading to the structural and functional defects of common COPD have not been sufficiently clarified for rational new drug development, and disease-modifying pharmacotherapy for common COPD currently is not available. In contrast to common COPD, both CF and AATD are monogenetic conditions associated with protein misfolding and gain or loss of function, and several of the mechanisms underlying their clinical manifestations have been identified. Recent research has pointed to links between CF and AATD on the one hand and common COPD on the other.

 

"Do AATD and CF inform COPD?" was recently asked at conference that brought together investigators with interest in either CF, AATD or common COPD and provided a forum for scientific discourse among them. The proceedings of the conference will be published in the Annals of the ATS Supplements.

 

The content highlighted not only phenotypic commonalities among the three conditions but also identified key pathogenic similarities, notably CFTR dysfunction, ER stress and lung cell apoptosis. Preliminary data presented at the conference suggest that agents currently reserved for the treatment of either CF or AATD could have a broader therapeutic spectrum. For example, drugs designed to restore CFTR function in CF could benefit COPD patients with or without AATD. Conversely, alpha-1 antitrypsin, which is administered for the treatment of AATD-related COPD, could benefit CF patients and COPD patients without AATD.

Feasibility and challenges of addressing this CQ or CC :

As Andre Cantin, a scientific committee member and speaker at the conference put it “All participants recognized the value of comparing these uncommon genetic diseases with the more common environmental disease COPD and felt that the research communities should enhance their dialogue. All also recognized that it is a challenging exercise to think of one’s data in the broader context of other diseases outside of one’s usual area – something we do not do enough”.

 

This, however, is not an insurmountable challenge. The NHLBI has the resources to solicit and sponsor such research that is likely to lead to new therapeutic solutions for common COPD, a condition for which disease modifying treatment currently is lacking.

 

This compelling questions lends specifically to the strategic goal of promoting basic and translational research that links CF and AATD to common COPD. Importantly though, this platform could apply to additional uncommon genetic conditions and the opportunity to inform common disease.

Name of idea submitter and other team members who worked on this idea : K. Erickson, A. Wanner, MD

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22 net votes
24 up votes
2 down votes
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Goal 3: Advance Translational Research

Epidemiology of Chronic Lung Disease

Develop large epidemiologic cohorts of subjects with various types of chronic lung diseases with long-term follow-up of elements of disease progression and of related co-morbidities. These cohorts should be the substrate for comprehensive studies of genetics, omics, and biomarkers, as well as for clinical trials.

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Detailed, high quality epidemiology of the major chronic lung diseases is seriously lacking. Very few cohorts of subjects at risk for or with chronic lung diseases have been established and as a result human data for understanding risk elements that determine disease progression and the development of new treatments for chronic lung diseases is substantially behind other fields. For example, COPD has become the third leading cause of death and is the only leading cause of death and disability that has increased in frequency consistently over the past several decades.

Feasibility and challenges of addressing this CQ or CC :

Multiple cohorts of Chronic Lung Diseases need to be established and support maintained for a large portion of the life of the cohort subjects in order to acquire the type of human data needed to address this challenge. An example of this challenge is that we know that GOLD 3 and GOLD 4 subjects have major disability and a markedly increased death rate, yet we know little about the elements that cause or are associated with risk of a GOLD 2 subject to progress to a GOLD 3 or GOLD 4 state.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and the COPDGene Executive Committee

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20 net votes
37 up votes
17 down votes
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Goal 3: Advance Translational Research

Animal Models for COPD -- Core Facilities

COPD is a major health problem with more than 140,000 deaths per year and yet there is a relative paucity of treatments that might modify the course of this disease. In part, this is due to the poor efficiency of animal models that require months of exposure to cigarette smoke. Moreover, there are no well validated small animal models of chronic mucus hypersecretion. Funding of core facilities that could both provide ...more »

Submitted by (@rwise0)

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

Details on the impact of addressing this CQ or CC :

Funding of core facilities that could both provide support for researchers wishing to study COPD, and the development of efficient research models as well as models of chronic bronchitis would be a major advance for screening for treatments of COPD.

Feasibility and challenges of addressing this CQ or CC :

Current technology is well established for exposure of small animals to combustible tobacco smoker. However there remains to be developed standardized exposures to e-Cigarettes and Biomass fuels.

Name of idea submitter and other team members who worked on this idea : Robert A. Wise

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20 net votes
24 up votes
4 down votes
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