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ARRA Investments in Asthma: Basic Research

Public Health Burden
Asthma is a chronic lung disease that affects more than 300 million people worldwide. Approximately 24.4 million Americans, including nearly 7 million children under 6 years of age, have asthma. 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. Through the ARRA, the NIH is supporting basic research to improve understanding of the causes of asthma and the factors that contribute to its progression.

Development and Severity: Environment, Genetics, and Genomics
While the exact cause of asthma remains unknown, it is believed to arise from a combination of environmental and genetic factors that may also contribute to the disparity of symptoms seen in patients of varying sex, race, and socioeconomic background. Multiple ARRA-funded grants have been awarded to study the cause and severity of asthma, including those designed to:
  • Identify the environmental factors underlying the development of asthma in children.1,2,3
  • Study the mechanisms by which specific proteins (i.e., Mfge84, Muc15 ) regulate asthma development and severity.
  • Determine the role of allergies in asthma by identifying genes that correlate with a higher risk for severe asthma6 and gaining insight into the mechanisms of allergic inflammation in order to identify new therapeutic targets. 7
The NIH also has awarded grants to support research to identify genes involved in the development of asthma, explore gene–gene and gene–environment interactions that lead to asthma and its clinical manifestations, and investigate genetic factors that influence individual responses to therapy. A few examples include research to:
  • Sequence the exome (the part of the genome that guides the production of proteins) of patients enrolled in established lung disease studies to improve understanding of the genetic basis for asthma susceptibility and variations in disease severity, and identify new therapeutic targets. 8
  • Combine genetic and genomic data from a large U.S.-based consortium to create one of the world’s largest collections of asthma-related biological materials and genomic data that will facilitate gene discovery and molecular studies for asthma over a range of ages, phenotypes, and races/ethnicities. The resource will be made widely available to asthma researchers through a centralized repository. 9,10,11
  • Identify genes and gene networks that regulate disease mechanisms in asthma and identify new targets for therapeutic intervention. 12
  • Investigate fetal epigenetic regulatory mechanisms (mechanisms that are inherited through a process other than changes to the underlying DNA sequence) in children enrolled in the longitudinal Infant Immune Study to define epigenetic signatures that determine childhood asthma and predict asthma status later in life. 13

Numerous ARRA-funded grants are supporting basic research on the immunobiology of asthma. Studies seeking to identify new molecular targets for interventions to prevent the onset of disease, and more effective treatments to reduce morbidity and mortality include those designed to:
  • Determine the role of specific immune cells, including natural killer T cells14, neutrophils15, and mast cells16, in asthma.
  • Study the ability of allergic mice to turn off their asthma in order to improve understanding of their how immune cells are able to inhibit airway inflammation, and potentially apply the findings to develop new treatments for asthma patients.17

  1. 3R01AI073964-02S1 -- Allergens in Inner-City Schools and Childhood Asthma -- Phipatanaul, Wanda
  2. 2R01AI035786-16 -- The Epidemiology of Home Allergens and Asthma -- Gold, Diane
  3. 3R56AI050681-06A2S1 -- Early Environmental Hygiene and Pediatric Asthma -- Johnson, Christine
  4. 1R21AI073988-01A1 -- Role of MUC1 in the Genesis of Allergic Asthma -- Kim, Kwang Chul
  5. 1R03AI081988-01 -- The Role of Mfge8 and Apoptotic Cell Clearance in Regulating Asthma Severity -- Atabai, Kamran
  6. 3U19AI070234-03S1 -- Epithelial Genes in Allergic Inflammation -- Khuranahershey, Gurjit
  7. 1R21AI076699-01A2 -- PGD2 Receptor Subtype Functions in T Cells from Asthmatics -- Loza, Matthew
  8. 1RC2HL102923-01 -- ARRA -- NHLBI Lung Cohorts Sequencing Project -- Bamshad, Michael J
  9. 1RC2HL101651-01 -- The EVE Asthma Genetics Consortium: Building Upon GWAS -- Ober, Carole
  10. 1RC2HL101543-01 -- The Asthma BioRepository for Integrative Genomics Research -- Raby, Benjamin Alexander
  11. 1RC2HL101487-01 -- Linking Genetics, Genomics and Phenomics to Better Understand Asthma Severity -- Meyers, Deborah
  12. 1RC1HL100315-01 -- Unbiased genome-wide screen to identify genes regulating mucous cell hyperplasia -- Whitsett, Jeffrey
  13. 1RC1HL100800-01 -- Epigenetic predicators of asthma in neonates -- Vercelli, Donata
  14. 2R01AI026322-18A2 -- Heterogeneity among Human CD4 T Lymphocytes -- Umetsu, Dale
  15. 1R21AI076760-01A2 -- Concentration Lock-on Microdevices for the Investigation of Neutrophil Chemotaxis -- Irimia, Daniel
  16. 1R03AI079471-01 -- Complement Protein Synthesis and Activation by Human Mast Cells -- Fukuoka, Yoshihiro
  17. 1R21AI079533-01A1 -- Regional B Cells Modulate Airway Th2 Responses -- Schramm, Craig

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