Pathogenesis and Genetics of Environmental Asthma Ozone Study
| Status: | Completed |
|---|---|
| Conditions: | Asthma |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 35 |
| Updated: | 11/8/2014 |
| Start Date: | July 2005 |
| End Date: | June 2012 |
| Contact: | W Michael Foster, PhD |
| Email: | foste028@mc.duke.edu |
| Phone: | 9196680382 |
Project 2: Genetic Regulation of Ozone Induced Inflammation in Humans.
The goals of the research are designed to accomplish genetic association studies of
candidate genes in healthy normal individuals exposed to 0.2 ppm for 2.25 hours with
intermittent exercise in order to search for associations between defined
genotypes/haplotypes and 3 specific in vivo respiratory endpoints: a) change in FEV1
immediately after ozone exposure; b) change nonspecific bronchial reactivity as reflected in
the change in methacholine PC20 FEV1 24 hours after ozone exposure ; and c) change in lung
epithelial integrity as reflected in the Clearance Halftime of technetium 24 hours after
ozone exposure. These studies have been carried forward to take place in 4 phases:
i) healthy individuals have been exposed to O3 using our standard exposure protocol; and we
will increase the numbers of individuals available for study.
ii) perform genetic association studies for the endpoints of spirometry (FEV1, FVC,
FEV1/FVC), PC20 FEV1 for methacholine, and epithelial integrity (Clearance Halftime) for 3
candidate O3 response genes taken from literature searches and/or previously characterized
to demonstrate associations. These physiologic endpoints have been examined in terms of
both a continuum of response, and discrete "responder" and "non-responder" endpoints.
candidate genes in healthy normal individuals exposed to 0.2 ppm for 2.25 hours with
intermittent exercise in order to search for associations between defined
genotypes/haplotypes and 3 specific in vivo respiratory endpoints: a) change in FEV1
immediately after ozone exposure; b) change nonspecific bronchial reactivity as reflected in
the change in methacholine PC20 FEV1 24 hours after ozone exposure ; and c) change in lung
epithelial integrity as reflected in the Clearance Halftime of technetium 24 hours after
ozone exposure. These studies have been carried forward to take place in 4 phases:
i) healthy individuals have been exposed to O3 using our standard exposure protocol; and we
will increase the numbers of individuals available for study.
ii) perform genetic association studies for the endpoints of spirometry (FEV1, FVC,
FEV1/FVC), PC20 FEV1 for methacholine, and epithelial integrity (Clearance Halftime) for 3
candidate O3 response genes taken from literature searches and/or previously characterized
to demonstrate associations. These physiologic endpoints have been examined in terms of
both a continuum of response, and discrete "responder" and "non-responder" endpoints.
Inclusion Criteria:
- Subjects with normal lung function values, and of normal body habitus (i.e., < BMI of
30);
- Do not have a history of lung disease, and not taking any medications for lung
disease or other clinical disorders, and no prior or current smoking history.
Exclusion Criteria:
- Non-willingness to sign a consent form for participation.
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