ARRA Investments in Asthma
Public Health Burden
Asthma is a significant chronic lung disease and public health burden, afflicting 22 million Americans, including nearly 7 million children under 6 years of age. Costs associated with asthma exceed $13 billion per year. Ethnic and racial disparities in asthma persist; minority communities have a higher prevalence of asthma and experience more severe disease. Currently there is no way to prevent or cure asthma. Existing treatments for asthma focus on controlling disease symptoms and preventing potentially life-threatening exacerbations. The goal of ARRA efforts in asthma research is to reduce the burden that asthma represents to all Americans by facilitating understanding of its causes and the factors that contribute to its progression and by developing new and improved treatment strategies.
Current standard-of-care therapy includes control of inflammation and bronchospasm by use of anti-inflammatory and bronchodilation agents. Asthma can be difficult to control despite recommended therapies because existing treatments only provide symptom relief without addressing the underlying disease. New preventive and disease-modifying therapies and diagnostics are needed. To promote the development of better therapies for asthma, ARRA-funded grantees are elucidating the underlying disease mechanisms and seeking to translate new knowledge into clinical research and more effective treatments. A few examples include studies to:
Enhance understanding of mucosal immune responses to microorganisms present in the respiratory tract and how the responses lead to respiratory inflammation and the development of chronic lung diseases, such as asthma and COPD.
Determine whether activation of an enzyme, acidic mammalian chitinase, affects the immune responses responsible for the type of inflammation seen in asthma.
Develop a noninvasive imaging method to evaluate regional inflammation in asthma and thereby enable more advanced studies of cellular interactions and biological pathways involved in asthma.
Develop a method to assess lung function using exhaled nitric oxide. The ability to use noninvasive metabolic markers of inflammation to guide clinical management of asthma would be a significant improvement over existing methods.
Develop innovative methods that use web-based technology to improve adherence to treatment recommendations in urban school settings.
Compare asthma-related outcomes resulting from a patient-advocate intervention to address health literacy to those resulting from standard asthma education approaches. An intervention addressing literacy could be easily incorporated into practice and may improve prevention of asthma exacerbations.
Asthma patients vary considerably in their disease manifestations and progression and in their response to treatments. Understanding this heterogeneity is essential not only for unraveling the causes of asthma but also for tailoring treatments to individuals and preventing disease. ARRA funding will enable a program using state-of-the-art genetic and genomic approaches to identify the genes and mutations involved in the development of asthma, to explore gene–gene and gene–environment interactions that lead to asthma and its different clinical manifestations and to investigate the genetic factors that influence individual responses to therapy. Genomic approaches such as gene expression profiling offer the possibility of classifying asthma into subtypes based on molecular signatures, enabling insights into disease development and severity, and potentially early diagnosis, improved prognosis, and personalized treatments. ARRA-funded investigators are seeking to identify genes associated with asthma, novel therapeutic targets, and determinants of asthma susceptibility, severity, and pharmacological responsiveness. A few examples include research to:
Sequence the exome (the part of the genome that guides the production of proteins) of patients in established lung disease studies to find genetic variants that may improve understanding of the genetic basis for asthma susceptibility and manifestations and identify new therapeutic targets.
Combine the genetic and genomic data from a large U.S.-based consortium, creating one of the world’s largest collections of asthma-related biological materials and genomic data for integrative genomics research, to increase the overall power for gene discovery and identification of molecular characterizations for asthma over a range of ages, phenotypes, severity, and races/ethnicities. This resource will be made widely available to other asthma researchers through a centralized repository.
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Identify genes and gene networks regulating disease mechanisms in asthma for therapeutic intervention.
Investigate fetal epigenetic (due to mechanisms other than from the DNA sequence) regulatory mechanisms in children enrolled in the longitudinal Infant Immune Study to define epigenetic signatures that determine childhood asthma and predict asthma status later in life.
-- Recognition of microbes by NKT cells at the lung mucosal surface -- Umetsu, Dale T (MA)
-- Understanding the role of AMCase in asthma -- Flavell, Richard A (CT)
-- Imaging Inflammation in Asthma -- Erzurum, Serpil (OH)
-- Exhaled Nitric Oxide: Mechanisms and Limitations -- George, Steven Carl (CA)
-- Using a Novel Technology to Improve Adherence: School-Based Asthma Treatment -- Halterman, Jill S (NY)
-- Patient Advocate and Literacy-based Treatment of Asthma --Apter, Andrea J (PA)
-- ARRA -- NHLBI Lung Cohorts Sequencing Project -- Bamshad, Michael J (WA)
-- The EVE Asthma Genetics Consortium: Building Upon GWAS -- Ober, Carole (IL)
-- The Asthma BioRepository for Integrative Genomics Research -- Raby, Benjamin Alexander (MA)
-- Linking Genetics, Genomics and Phenomics to Better Understand Asthma Severity -- Meyers, Deborah (NC)
-- Unbiased genome-wide screen to identify genes regulating mucous cell hyperplasia -- Whitsett, Jeffrey (OH)
-- Epigenetic predicators of asthma in neonates -- Vercelli, Donata (AZ)
Page Last Updated on June 30, 2018
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