Dissertation/Thesis Abstract

The author has requested that access to this graduate work be delayed until 2019-07-17. After this date, this graduate work will be available on an open access basis.
The Relationship of Genes and Environment with Exhaled Nitric Oxide in Children with Asthma
by Spanier, Adam Jason, Ph.D., University of Cincinnati, 2008, 138; 10631277
Abstract (Summary)

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.

Indexing (document details)
Advisor:
Commitee: Buncher, Ralph, Hornung, Richard, Lanphear, Bruce, Lierl, Michelle, Rinsky, Robert
School: University of Cincinnati
Department: Epidemiology
School Location: United States -- Ohio
Source: DAI-B 78/11(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Epidemiology, Environmental science, Health care management
Keywords: Asthma, Environment, Exhaled nitric oxide, Nitric oxide synthase, Pediatric, Polymorphism
Publication Number: 10631277
ISBN: 9780355015454