Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00018096
Status:
COMPLETED
Last Update Posted:
2008-05-06
First Post:
2001-07-02
Brief Title:
The Genetics of Environmental Asthma
Sponsor:
National Institute of Environmental Health Sciences NIEHS
Organization:
National Institute of Environmental Health Sciences NIEHS
Study Overview
Official Title:
The Genetics of Environmental Asthma
Status:
COMPLETED
Status Verified Date:
2008-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In this project we hypothesize that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma To test this hypothesis we identify the genes that are differentially expressed by airway epithelial cells following challenge with stimuli that induce acquired house dust mite or innate LPS immune responses and then determine whether polymorphisms in these genes are associated with the development of asthma in a separate well characterized familial cohort of asthmatics This is a powerful approach that is designed to identify novel genes that are associated with both asthma pathogenesis differentially expressed in the exposure-response study and asthma susceptibility genetically associated with asthma in a linkageassociation study
Detailed Description:
The overall goal of this project is to identify genes that are involved in the development of airflow obstruction and airway inflammation in asthmatics and to determine whether polymorphisms in these differentially expressed genes predispose individuals to develop asthma Asthma is a complex genetic disorder that is caused by a number of unique gene-gene and gene-environment interactions The search for asthma susceptibility genes has been complicated by the broad clinical phenotype of asthma the polygenic inheritance pattern of this disease and the substantial role of environmental exposures in the development and progression of asthma Inhaled environmental agents induce several biologic responses in asthmatics including the induction of acquired and innate immunity that leads to acute and chronic forms of airway inflammation and airway remodeling Acquired immune responses to protein antigens such as house dust mite allergen often induce type 2 T lymphocyte-driven responses Th2 which appear to be important in atopic asthma Recent studies by our group and others demonstrate that innate immunity initiated by inhalation of bacterial and viral pathogens organic dusts endotoxin or lipopolysaccharide LPS air pollution particulate matter and ozone can also cause acute and chronic forms of airflow obstruction airway inflammation and even airway remodeling Emerging evidence indicates that both acquired and innate immune responses in the lung may be influenced by polymorphic genes For instance functional polymorphisms in the IL-4 receptor gene are thought to preferentially stimulate acquired Th2 immune responses to inhaled allergens and we have recently shown that common co-segregating mutations in TLR4 a transmembrane receptor for LPS are associated with diminished airway responsiveness to inhaled LPS These observations suggest that environmental challenges can be used to narrow the phenotype of asthma and investigate genetic susceptibility in biologically specific forms of asthma
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2357 | None | None | None |