Asthma is the most common chronic and disabling disease of childhood. There are no simple, noninvasive measures of airway inflammation to help guide physicians in the medical management of children with asthma. Exhaled nitric oxide (eNO), a measure that increases with airway inflammation, has been proposed as such a tool to manage childhood asthma; however, there are gaps in our knowledge about eNO that must be filled before it can be used as a clinical tool in asthma management. This study will explore how environmental exposures and polymorphisms in nitric oxide synthase genes may affect eNO levels in children with asthma. In addition, we will examine the relationship of eNO levels with number of asthma exacerbations, reported healthcare utilization, and a validated quality of life index (Child Health Survey for Asthma). This proposed secondary analysis uses data from the Cincinnati Asthma Prevention (CAP) study (R01-HL65731-01), a longitudinal, NHLBI-funded trial of HEPA-CPZ air cleaners. The CAP study involved 225 children, 6 to 12 years of age, who had doctor diagnosed asthma and were exposed to environmental tobacco smoke (ETS). Numerous measures of environmental exposure (e.g. settled indoor allergens, biomarkers of ETS exposure, and air nicotine levels) and asthma severity were collected during the year long study period. The objectives of this application are to evaluate the longitudinal effects of environmental and genetic factors on eNO levels and to examine the association of eNO with asthma severity. To achieve our objectives we will complete the following aims:
Aim 1 : To determine the longitudinal relationship of environmental exposures (sensitization and exposure to indoor allergens) with eNO levels over the 12 month study period.
Aim 2 : To evaluate whether polymorphisms in NOS genes are associated with eNO levels as measured over the twelve month study period and whether environmental exposures modify this relationship.
Aim 3 : To determine the relationship of eNO levels and asthma severity over a 12 month period. This analysis is innovative because to our knowledge no studies have examined the relationship of multiple environmental exposures and genetic polymorphisms with eNO in asthmatic children using a longitudinal study design. This proposed exploratory study is relevant because it offers a unique opportunity to translate epidemiologic data about eNO from the research arena to clinical practice. If this and other studies demonstrate the utility of eNO, it would enhance our ability to manage disease and improve the quality of life for children who have the most disabling disease of childhood. ? ? ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-IRAP-Q (01))
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Banks-Schlegel, Susan P
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Cincinnati Children's Hospital Medical Center
United States
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Spanier, Adam J; Kahn, Robert S; Hornung, Richard et al. (2011) Associations of Fraction of Exhaled Nitric Oxide with Beta Agonist Use in Children with Asthma. Pediatr Allergy Immunol Pulmonol 24:45-50
Spanier, Adam J; Kahn, Robert S; Hornung, Richard W et al. (2009) Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children. Pediatr Pulmonol 44:812-9
Spanier, Adam J; Hornung, Richard W; Kahn, Robert S et al. (2008) Seasonal variation and environmental predictors of exhaled nitric oxide in children with asthma. Pediatr Pulmonol 43:576-83