Showing 3 ideas for tag "phenotypes"

Goal 2: Reduce Human Disease

Define the biological basis, new diagnostics and therapeutics for severe sarcoidosis phenotypes

Sarcoidosis affects individuals of all races and ages and both genders, although it tends to cause significant morbidity and mortality for people in the prime of their productive life. Women, minorities and underserved populations tend to be more affected. Recent studies suggest that sarcoidosis and its severe manifestations, such as cardiac, neurologic and end stage pulmonary disease' are increasing, While the current... 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

Increasing our understanding of the biological basis of sarcoidosis, its more severe phenotypes, and resolution of disease, will help improve detection and personalized management and treatment of this disease, ultimately reducing disease burden. With the current availability of epidemiologic, genetic, genomic and epigenetic tools and studies, as well as buy in from sarcoidosis patient groups, we are poised to address why some people develop more severe forms of this disease. While genetic variants are associated with sarcoidosis, the specific variants responsible for disease risk and that dictate disease activity are largely unknown. The results of studies to date suggest that other susceptibility factors or forms of genetic regulation must act in concert with exposure in the development of sarcoidosis. Growing data in other immune-mediated diseases suggests that epigenetic mechanisms in combination with genetic susceptibility and environment may help explain disease risk. By understanding these genetic, genomic and epigenetic factors, and better defining the natural history of sarcoidosis, interventions can be tested and undertaken to potentially prevent or treat the development and or progression of this devastating disease.

Feasibility and challenges of addressing this CQ or CC

The care and management of individuals with sarcoidosis is not well standardized. This has been hampered by a lack of understanding of the natural history, which appears to vary significantly. As a result, undertaking studies to define the pathobiology of this disease is biased based on the centers and researchers involved. There have been few limited multi-center studies of sarcoidosis, except for pharmaceutical trials. In the past few years, NHLBI has funded the GRADS study, a cross-sectional multi-center study, laying the ground work for needed longitudinal multi-center studies of the biological basis of disease. With involvement from a larger sarcoidosis research community and the ability to undertake large scale studies to not only define the epidemiology of this disease, but also the pathobiology of disease based on integrative Omics, new personalized diagnostics and therapeutics can be developed and tested to help address the burden of sarcoidosis.

Name of idea submitter and other team members who worked on this idea Lisa Maier, Nabeel Hamzeh, Tasha Fingerlin, Ivana Yang, Brian O'Connor, Elliott Crouser

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Goal 2: Reduce Human Disease

what are the molecular pheontypic differences in IPF/ILD

What are the molecular phenotypic differences in blood and tissue of IPF ILD and how do they relate to disease course and potential response to therapy. There is a need to gain understanding in humans of the differences and similarities in iPF and iLD in general to eliminate the idiopathic nature and establish human targets. The challenge is coupling such research to longer term studies/outcomes and potentially clinical... 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

Establishing molecular definitions for this idiopathic disease would a) provide greater clarity and definition to a what is otherwise a syndrome b) establish targets for intervention both for IPF and ILD in general c) refocus translational efforts on human setting for this purely human disease d) establish molecular relationships between IPF and outcomes e) establish intermediate biomarkers for more rapid evaluation for treatment development f) allow potential crossover development with acute lung injury fibrosis g) establish molecular relationships for crossover with human immunology studies and other autoimmune diseases with fibrotic tissue development (CAD, Glomerulonephritis, etc).

Feasibility and challenges of addressing this CQ or CC

Challenges surround lack of a larger more comprehensive and integrative approach to studying human disease. In an uncommon disease such as IPF, mutlicenter patient enrollment and biologics acquisition must occur in conjunction with both long term longitudinal outcomes and the influence of both new standard of care therapies and novel clinical trials. The scope of studies must be larger, more pragmatic and longer than previously designed NIH clinical studies to allow for integration of translational research. The challenge surrounds failure to allow these elements to coexist. The potential very large for true ILD program with a vision for a long term integrative plan with vision rather than just individual RO1 efforts. An example would an overriding longitudinal study in which patients could enroll and participate in other projects/studies/treatment but where the patient is never lost to follow up. This as cornerstone would then allow other programatic efforts to coexist.

Name of idea submitter and other team members who worked on this idea Imre Noth

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Goal 2: Reduce Human Disease

Heterogeneity in Asthma Phenotypes

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

Asthma appears to be due to heterogenous etiologies.  To better characterize the various phenotypes and potential etiologies, it would be important to create more epidemiologic and biomarker focused databases, which could... more »

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

Name of idea submitter and other team members who worked on this idea Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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