Showing 77 ideas for tag "lung"

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?

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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Goal 1: Promote Human Health

Environmental stimuli and the lung: predictors of homeostatic or pathological responses

What are the molecular and cellular responses in the lung that occur after environmental stimuli that predict homeostatic resilience or transition to disease, disorder, or aging?

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

Details on the impact of addressing this CQ or CC

Addressing this line of research could define biomarkers and pathways useful for prediction of how human response to an external stimulus of varied nature (i.e. microorganism, chemical, physical) could lead to specific outcomes in relationship to the duration of the exposure and the genetic makeup of the individual exposed. Identification of early signals and the pathways involved could lead to novel preventative or therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

Methods for systems biology approaches to address complex pathobiological iterations are ready to be exploited to answer these questions.
Great progress has been made in the clarification of basic mechanisms of molecular and cellular response to environmental stimuli, in cross-sectional analyses. The continuum of the response in relationship to the genetic background of individuals responding with a homeostatic or pathological long-term outcome is missing from these data.

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

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Goal 2: Reduce Human Disease

Mechanisms for sex-specific differences in lung diseases

What molecular and cellular pathways explain the sex-specific differences in the prevalence, severity, and progression of lung diseases?

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

Details on the impact of addressing this CQ or CC

Understanding the molecular and cellular bases of differences in prevalence and outcomes of lung diseases will offer insight into disease mechanisms and help to address disease disparities. Some potential bases for disparities, such as differences in hormone levels between men and women, could potentially be therapeutically modulated to mitigate the effects of disease.

Feasibility and challenges of addressing this CQ or CC

The increased understanding of lung cell biology, along with a renewed focus on sex and gender differences, make this the perfect time to start addressing these questions.
Multiple diseases affecting the lung, such as LAM (lymphangioleiomyomatosis), sarcoidosis, asthma, and COPD, have distinct prevalence or associated mortality in a sex-dependent manner. The reasons for these differences are still unknown.

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

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18 up votes
12 down votes
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Goal 2: Reduce Human Disease

Fetal basis for Adult Disease

Maternal exposures during pregnancy have the potential to alter development and lead to lifelong susceptibility to disease. There is epidemiological evidence of this in the asthma field, where maternal smoking leads to increased asthma rates. However, the molecular mechanisms by which maternal exposures cause lung disease later in life are not known and the influence of in utero exposures on susceptibility to lung cancer,... more »

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

Details on the impact of addressing this CQ or CC

Addressing the impact of maternal exposures on fetal lung disease would make a major impact on human health by giving regulatory agencies the data they need to make educated decisions with respect to issues such as nicotine regulation, air pollution, water pollution, and other sources of maternal exposures.

Feasibility and challenges of addressing this CQ or CC

With the established animal and stem cell models of development, this research is immediately feasible.

Name of idea submitter and other team members who worked on this idea Diane Carlisle

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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest.

Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells... more »

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

Details on the impact of addressing this CQ or CC

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

Name of idea submitter and other team members who worked on this idea Jalees Rehman

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11 up votes
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Goal 2: Reduce Human Disease

Low-dose and non-ionizing imaging for chronic lung disease

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Imaging plays a crucial role in the initial evaluation of patients with suspected or surveillance of those with confirmed diffuse chronic lung disease. Attention towards developing alternative non-ionizing imaging technologies and evaluating the efficacy of radiation dose saving techniques will impact a large patient population.

Feasibility and challenges of addressing this CQ or CC

Imaging, particularly computed tomography (CT) plays a major role in the evaluation of diffuse pulmonary disease. High resolution CT (HRCT) characterizes parenchymal patterns of lung disease, identifies areas amenable to biopsy, and aids in decisions pertaining to workup and therapy of lung disease. With multidetector CT technology, volumetric HRCT enables evaluation of the entire lung volume for diffuse lung disease. The utility of CT needs to be balanced with the exposure of patients to ionizing radiation, particularly younger-aged individuals who are more sensitive to ionizing radiation. In CT, dose-saving techniques enable imaging of the parenchyma at ultra-low dose levels. Additionally, an understanding of low radiation-dose CT techniques that preserve the diagnostic ability for diffuse lung disease, while maintaining the precision of quantitative measures, is needed. Magnetic resonance imaging (MR) is underutilized as an imaging tool given respiratory motion and limitations in spatial resolution. A need exists to develop and apply MR imaging techniques with spatial resolution approaching that of high resolution CT. Promising advances in the MR technology has occurred, and continued development and application will provide alternative and non-ionizing options for imaging patients with diffuse lung disease affecting both the parenchyma and airways.

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

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Goal 1: Promote Human Health

Control of the molecular and cellular characteristics of regional variations in the lung

What are the regional variations in cellular and molecular characteristics (from epigenetics to microbiome) in the lung, and what controls these variations?

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

Details on the impact of addressing this CQ or CC

Advance in this research will help to understand the heterogeneity of lung disease

Feasibility and challenges of addressing this CQ or CC

Novel technologies, e.g. single cell analysis and imaging have been developed to get high resolution characterization of the cells in the lung.
Many lung diseases are heterogeneous with regional variations, which are not fully characterized at the molecular and cellular level. Mechanisms underlying the formation of the regional variations are also poorly understood.

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

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12 up votes
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Goal 1: Promote Human Health

Sleep Effects on Lung Biology

What sleep patterns contribute to normal lung growth, development, and metabolism from birth through childhood, lung health during middle-age, and senescence of lung tissues in the elderly?

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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3 net votes
16 up votes
13 down votes
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Goal 2: Reduce Human Disease

Systems Approaches to "Phenosimilar" Diseases

There are diverse diseases that share similar features. For example, many chronic airways diseases (chronic aspiration, ciliary dyskinesia, some COPD) "phenocopy" cystic fibrosis in terms of infectious agents, mucus clearance problems, progressive loss of lung function, etc. Use multiplatform "omics" approaches and Big Data bioinformatics to identify common nodes for therapeutic targeting. Other examples: emphysema and... more »

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

Details on the impact of addressing this CQ or CC

may be able to target multiple diseases with new or repurposed therapies. Might narrow down the broad array of potential "high value" targets to study.

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12 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 »

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

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Goal 2: Reduce Human Disease

Reversing pulmonary fibrosis/interstitial lung disease

Can a multipronged approach to reversing/repairing scar tissue in pulmonary fibrosis be deployed as soon as possible?

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

Details on the impact of addressing this CQ or CC

Despite high mortality rates and frustrating disease management marked by exacerbations and uncertainty including chronic oxygen supplementation, pulmonary fibrosis patients lack evidence-based treatments to reverse and repair the fibrotic process. These patients comprise a comparatively smaller proportion of lung disease patients such as chronic obstructive pulmonary disease and asthma and owing to their smaller number, have not been studied in large-scale randomized controlled trials. Treatments that need to be critically studied include regenerating lung tissue through stem cell treatment, artificial/ mechanical lung (augmentation) technology, and new drugs to directly reverse scar tissue, not simply to arrest the fibrotic process as with the two new available drugs for IPF patients.

Feasibility and challenges of addressing this CQ or CC

Challenges are smaller numbers of available patients available for clinical trials compared with other lung conditions such as COPD and asthma and lack of research funding. Also the etiology of the disease is multifactorial and the categories of fibrosis difficult to accurately diagnose and understand.

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

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Goal 2: Reduce Human Disease

Quantitative imaging biomarkers for chronic lung disease

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Methods for stratifying patients with diffuse lung disease are crucial for predicting their clinical course and directing appropriate therapies accordingly. Currently imaging markers for prognostic stratification are limited, due to observer variability in characterizing the type and degree of computed tomography (CT) abnormalities. A reproducible method for categorizing varying diffuse lung diseases on CT imaging is needed, particularly in combination with other biomarkers in a multidisciplinary approach. With lung cancer screening, the characterization and stratification of patients with varying COPD phenotypes and interstitial lung disease are essential to aid in management of the large number of patients who currently satisfy criteria for CT lung cancer screening.

Feasibility and challenges of addressing this CQ or CC

Currently the classification of diffuse lung disease on CT is based upon visual evaluation and qualitative or semi-quantitative evaluation of CT data. Diffuse lung disease manifests with varying CT findings and distribution within the lung. Computer-assisted tools for quantifying airways and parenchymal disease have been developed. More-sophisticated quantitative computer image-analysis methods, such as those that address three-dimensional spatial orientation, are possible given advances in computer capabilities yet remain in need of further development. Advances in magnetic resonance imaging (MR) technology, positron emission tomography (PET), and PET/MR will increase the ability to characterize diffuse lung disease quantitatively. The ability of such technology to differentiate subtypes within more frequently occurring and clinically-significant diffuse lung disease is feasible. Such tools would impact a large population, particularly given the potential need to phenotype emphysema and smoking-related interstitial pneumonias in those undergoing CT screening.

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

Imaging indicators of metabolic syndrome and cardiopulmonary disease

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

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

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