Asthma is a disease of great clinical importance and increasing prevalence. Its pathogenesis has not been well-understood because of the phenotypic heterogeneity of the disease, the heterogeneity of underlying biology, and the critical role played by environmental exposures. It is conceivable that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma. To investigate this hypothesis, human subjects with well characterized allergy, mild asthma, both or neither will be recruited and challenged bronchoscopically with airway instillation of saline, house dust mite antigen, and lipopolysaccharide. Post-challenge inflammatory and epithelial cells will be collected from these patients and analyzed, with particular focus on gene expression array data. Candidate asthma susceptibility genes will be identified through gene expression, and gene association studies will be performed by comparing our sample population to other asthma populations. Candidate genes will then by analyzed for sequence polymorphisms in asthmatics. This model of airway disease is a potentially very powerful tool to elucidate important gene-environment interactions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL082055-01
Application #
6995021
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Rothgeb, Ann E
Project Start
2005-07-25
Project End
2006-06-30
Budget Start
2005-07-25
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$51,281
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Yang, Ivana V; Tomfohr, John; Singh, Jaspal et al. (2012) The clinical and environmental determinants of airway transcriptional profiles in allergic asthma. Am J Respir Crit Care Med 185:620-7