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1.  Seasonal Variation and Environmental Predictors of Exhaled Nitric Oxide in Children with Asthma 
Pediatric pulmonology  2008;43(6):576-583.
Summary
The fraction of exhaled nitric oxide (FeNO), a measure of airway inflammation, shows promise as a noninvasive tool to guide asthma management, but there is a paucity of longitudinal data about seasonal variation and environmental predictors of FeNO in children. The objective of this project was to evaluate how environmental factors affect FeNO concentrations over a 12-month study period among children with doctor diagnosed asthma. We conducted a prospective cohort study of 225 tobacco-smoke exposed children age 6 to 12 years with doctor-diagnosed asthma including measures of FeNO, medication use, settled indoor allergens (dust mite, cat, dog, and cockroach), and tobacco smoke exposure. Baseline geometric mean FeNO was 12.4 ppb (range 1.9 to 60.9 ppb). In multivariable analyses, 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. In secondary analyses of allergen sensitization, only sensitization to dust mite and cat were associated with increased FeNO levels. Our data demonstrate that FeNO levels over a year long period reflected baseline FeNO levels, allergen sensitization, season, and inhaled steroid use in children with asthma. These results indicate that FeNO levels are responsive to common environmental triggers as well as therapy for asthma in children. Clinicians and researchers may need to consider an individual’s baseline FeNO levels to manage children with asthma.
doi:10.1002/ppul.20816
PMCID: PMC3483596  PMID: 18429012
allergen; sensitization; tobacco smoke; inhaled corticosteroid
2.  The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research 
Background
Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking.
Methods
In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset.
Results
To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases.
Conclusions
The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients.
doi:10.1089/ped.2011.0116
PMCID: PMC3377950  PMID: 22768387
3.  Effects of HEPA Air Cleaners on Unscheduled Asthma Visits and Asthma Symptoms for Children Exposed to Secondhand Tobacco Smoke 
Pediatrics  2010;127(1):93-101.
OBJECTIVE:
The goal was to test the effects of high-efficiency, particulate-arresting (HEPA) air cleaners on unscheduled asthma visits and symptoms among children with asthma exposed to secondhand smoke.
METHODS:
We enrolled 225 eligible children who were 6 to 12 years of age, had physician-diagnosed asthma, and were exposed to ≥5 cigarettes per day. We conducted a double-blind, randomized trial. Children were assigned randomly to receive 2 active or inactive HEPA air cleaners.
RESULTS:
Of 225 enrolled children, 110 (49%) were assigned to the intervention group and 115 (51%) to the control group; 215 (95%) completed the trial. During the trial, there were 42 fewer unscheduled asthma visits among children in the intervention group (18.5% [95% confidence interval: 1.25%–82.75%]; P = .043), compared with those in the control group, after adjustment for baseline differences. There was a significant difference in the reductions of levels of particles of >0.3 μm according to group assignment; there was a 25% reduction in particle levels in the intervention group, compared with a 5% reduction in the control group (P = .026). There were no significant differences in parent-reported asthma symptoms, exhaled nitric-oxide levels, air nicotine levels, or cotinine levels according to group assignment.
CONCLUSIONS:
These results hold promise for using HEPA air cleaners as part of a multifaceted strategy to reduce asthma morbidity, but further research is necessary before they can be recommended routinely for the medical management of asthma.
doi:10.1542/peds.2009-2312
PMCID: PMC3010094  PMID: 21149427
asthma; children; secondhand smoke; air cleaner; randomized controlled trial; unscheduled asthma visits; exacerbations
4.  Associations of Fraction of Exhaled Nitric Oxide with Beta Agonist Use in Children with Asthma 
The fraction of exhaled nitric oxide (FeNO), a measure of airway inflammation, is a potential noninvasive tool to guide asthma management in children. It remains unclear, however, if FeNO adds any information beyond clinical assessment of asthma control. We evaluated the associations of FeNO level with short acting beta agonist use and compared it with other clinical asthma assessments. We examined a prospective cohort study of 225 tobacco-smoke-exposed children aged 6–12 years with doctor-diagnosed asthma, including measures of FeNO, reported days of short acting beta agonist use, and unscheduled asthma visits. FeNO was analyzed in relation to current and future (3 months later) short acting beta agonist use. Mean FeNO at baseline, 6, and 12 months was 15.5, 15.7, and 16.8 ppb. In multivariable analyses, higher FeNO level was associated with increased short acting beta agonist use but only among children who were not on inhaled corticosteroids. Among those not on an inhaled steroid, there was a 12% increase in current and 15% increase in future days of short acting beta agonist use for every 10 ppb increase in FeNO level. FeNO levels remained associated with current short acting beta agonist use even after adjusting for unscheduled asthma visits. FeNO levels remained associated with future short acting beta agonist use even after adjusting for current short acting beta agonist use or unscheduled asthma visits. We conclude that FeNO levels are associated with short acting beta agonist use but only among children who are not on an inhaled corticosteroid.
doi:10.1089/ped.2010.0047
PMCID: PMC3255503  PMID: 22276224
5.  Environmental Exposures, Nitric Oxide Synthase Genes, and Exhaled Nitric Oxide in Asthmatic Children 
Pediatric pulmonology  2009;44(8):812-819.
Summary
Exhaled nitric oxide (FeNO), a measure of airway inflammation, is being explored as a tool to guide asthma management in children. Investigators have identified associations of genetic polymorphisms in nitric oxide synthase genes (NOS1 and NOS3) with FeNO levels; however, none have explored whether these polymorphisms modify the relationship of environmental exposures with FeNO. The objective of this project was to evaluate the association of NOS polymorphisms and environmental exposures with FeNO levels among children with asthma. We conducted a 12 month, prospective cohort study of 225 tobacco-smoke exposed children (6 to 12 years) with doctor-diagnosed asthma. We assessed environmental exposures (tobacco, indoor allergens, & airborne particulates), polymorphisms in NOS1 (an intronic AAT tandem repeat) and NOS3 (G894T), and FeNO levels. There was no association of NOS1 or NOS3 polymorphisms with FeNO levels. There were no significant interactions of environmental exposures and the NOS1 polymorphism with FeNO levels. In contrast, there was an interaction of the NOS3 polymorphism and airborne nicotine concentration with FeNO levels (p=0.01). Among GG genotype individuals, nicotine exposure did not affect FeNO levels; however, among individuals with at least one T allele, higher nicotine exposure was associated with lower FeNO levels (approximately 5ppb decrease from the lowest to the highest quartile). We conclude that genetic differences may explain some of the conflicting results in studies of the effects of tobacco smoke exposure on FeNO levels and may make FeNO interpretation difficult for a subset of children with asthma.
doi:10.1002/ppul.21071
PMCID: PMC2857409  PMID: 19603529
allergen; asthma; sensitization; tobacco smoke; air nicotine; nitric oxide synthase; inhaled corticosteroid; exhaled nitric oxide

Results 1-5 (5)