Recurrent wheezing is common in early childhood, affecting over 20% of children. Noninvasive methods to diagnosis airflow obstruction and airway inflammation are lacking in infants and toddlers, making it difficult for clinicians to separate transient wheezing of early childhood from early persistent asthma. If such methods were available they would assist medical care providers with the early diagnosis of asthma, provide a rationale basis for the initiation of daily inhaled corticosteroids, and perhaps reduce early decline in lung function through timely therapeutic intervention. The overall goal of this research is to characterize longitudinal noninvasive measures of airway inflammation and airflow obstruction in a cohort of infants with a history of recurrent wheezing/and age- matched healthy infants. Dr. Debley will assess the associations of longitudinal measurements of exhaled nitric oxide, cysteinyl leukotrienes in exhaled breath condensate, and the thoracic index (an anthropometric measure of pulmonary hyperinflation), with symptoms and infant pulmonary function measures using the raised-volume rapid thoracic compression technique. He will also compare longitudinal values of these noninvasive measures between infants with recurrent wheezing and infants without respiratory symptoms. Dr. Debley's career goal is to become a leader within the subspecialty of pediatric pulmonology in the study of children with recurrent wheezing, with particular expertise in the non-invasive assessment of airflow obstruction and airway inflammation in young children. He proposes a rigorous 5 year career development plan supervised by four outstanding and experienced mentors, which will provide him with enhanced skills and knowledge in several new areas relevant to his research plan and career goals, including: the performance and interpretation of infant lung function using the raised-volume thoracic compression technique, the collection of exhaled breath condensate and analysis of its constituents, the application of statistical methods used to analyze longitudinal data, a comprehensive understanding of nitric oxide biology including the analysis of exhaled nitric oxide in young children, and a detailed understanding of inflammatory mediators in asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
3K23HL077626-04S1
Application #
7691866
Study Section
Special Emphasis Panel (ZHL1-CSR-M (M1))
Program Officer
Rothgeb, Ann E
Project Start
2005-08-01
Project End
2009-07-31
Budget Start
2008-09-26
Budget End
2009-07-31
Support Year
4
Fiscal Year
2008
Total Cost
$28,633
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
Elliott, M; Heltshe, S L; Stamey, D C et al. (2013) Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers. Clin Exp Allergy 43:1351-61
Lopez-Guisa, Jesus M; Powers, Claire; File, Daniele et al. (2012) Airway epithelial cells from asthmatic children differentially express proremodeling factors. J Allergy Clin Immunol 129:990-7.e6
Debley, Jason; Stanojevic, Sanja; Filbrun, Amy G et al. (2012) Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors. Pediatr Pulmonol 47:421-8
Debley, Jason S; Cochrane, Elizabeth S; Redding, Gregory J et al. (2012) Lung function and biomarkers of airway inflammation during and after hospitalization for acute exacerbations of childhood asthma associated with viral respiratory symptoms. Ann Allergy Asthma Immunol 109:114-20
Debley, Jason S; Ohanian, Arpy S; Spiekerman, Charles F et al. (2011) Effects of bronchoconstriction, minute ventilation, and deep inspiration on the composition of exhaled breath condensate. Chest 139:16-22
Ohanian, Arpy S; Zimmerman, Jerry; Debley, Jason S (2010) Effects of sample processing, time and storage condition on cysteinyl leukotrienes in exhaled breath condensate. J Breath Res 4:046002
Debley, Jason S; Stamey, David C; Cochrane, Elizabeth S et al. (2010) Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlers. J Allergy Clin Immunol 125:1228-1234.e13
Debley, Jason S; Hallstrand, Teal S; Monge, Tito et al. (2007) Methods to improve measurement of cysteinyl leukotrienes in exhaled breath condensate from subjects with asthma and healthy controls. J Allergy Clin Immunol 120:1216-7