Asthma is the most common chronic and disabling disease of childhood. Unfortunately, there are limited tools for primary care asthma management, and these tools are poor predictors of a patient's disease status, airway inflammation, and future disease. The first part of the dissertation reviews the inflammatory biomarkers that are currently being investigated as potential tools to assess airway inflammation in children with asthma. Of these exhaled markers, the most data is available for exhaled nitric oxide (FeNO).
The second part of the dissertation details an evaluation of the association of environmental exposures and FeNO levels among children with asthma. Higher baseline FeNO levels, atopy, and fall season were associated with increased FeNO levels, measured 6 and 12 months after study initiation, whereas inhaled steroid use, summer season, and increasing nicotine exposure were associated with lower FeNO levels. This suggests that FeNO is responsive to some of the same moderators and risk factors associated with asthma control.
Genetic differences influence the susceptibility and response to environmental exposures. The third part of the dissertation provides information on basic genetic epidemiology. This information will help interpret the fourth part of the dissertation, an exploration of the association of nitric oxide synthase genes (NOS) and environmental exposures with FeNO levels among children with asthma. There was no association of genetic polymorphisms in NOS1 or NOS3 with FeNO levels in this cohort. Individuals with the GT or TT genotypes of NOS3 had decreased FeNO when exposed to nicotine. The differing genetic susceptibilities may explain some of the conflicting results in studies that evaluated the effects of tobacco exposure on FeNO levels without considering genetic differences. Together these findings suggest that FeNO holds promise for use in the management of asthma in children.
|Commitee:||Buncher, Ralph, Hornung, Richard, Lanphear, Bruce, Lierl, Michelle, Rinsky, Robert|
|School:||University of Cincinnati|
|School Location:||United States -- Ohio|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Subjects:||Epidemiology, Environmental science, Health care management|
|Keywords:||Asthma, Environment, Exhaled nitric oxide, Nitric oxide synthase, Pediatric, Polymorphism|
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