This application is based in large measure on the candidate's prior experience in treating children with asthma in a small developing island-nation where the incidence of asthma is rapidly increasing. This experience deeply motivated the candidate to obtain in-depth knowledge into both the epidemiology and pathophysiology of pedjatric asthma. The candidate's goal is to pursue independent investigation into the mechanisms responsible for this burgeoning pediatric illness. At the University of California, Irvine, the candidate selected as co-mentors two physician scientists whose research in: 1) air pollution and pediatric asthma;and 2) immune responses to exercise in children complemented one another. The rationale for this collaboration is that both air pollution and exercise exacerbate asthma in children, but the mechanisms that link these two phenomena are not clear. It is known that exercise even in healthy children leads to a robust activation of innate immunity with increases in neutrophils, neutrophil adhesion molecules, and neutrophit oxidative stress mechanisms that play a role in bronchoconstriction. Air pollution sensitizes neutrophils rendering them more prone to release these factors when environment factors, similar to exercise, stimulate innate immunity. Intriguingly, both exercise and pollution also affect lymphocyte TH1/TH2 polarization, now known to influence neutrophil function. Despite these compelling observations, little is known about neutrophil responses to exercise in the child with asthma, or the association to lymphocyte TH1/TH2 balance, and this is the focus of the proposed research. A major stumbling block in research in pediatric asthma has been the difficulty in truly characterizing disease severity. This study proposes to identify a cohort of children with persistent asthma whose clinical severity and air pollution exposure will be measured comprehensively under field conditions using nephelometry and spirometry to investigate new disease mechanisms using laboratory based, precisely controlled exercise challenges focused on neutrophil function and the association to lymphocyte TH1/TH2 balance. Neutrophil function will be assessed from the level of neutrophil genomic expression to systemic manifestations of neutrophil oxidative stress responses. The lymphocyte TH1/TH2 balance will be assessed by intracellular cytokine profiles. To complement the research project, the candidate has developed a robust didactic program including formal courses in statistics, molecular biology, and epidemiology;and ongoing postgraduate seminar series in exercise physiology and immunology. Finally, the candidate's career development will be overseen by the project co-mentors and a distinguished advisory committee consisting of immunologists, exercise physiologists, and biostatisticians.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23ES014923-04
Application #
7531043
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Shreffler, Carol K
Project Start
2006-01-01
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
4
Fiscal Year
2009
Total Cost
$151,632
Indirect Cost
Name
University of California Irvine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Abosaida, Alladdin; Chen, Jen Jen; Nussbaum, Eliezer et al. (2015) Vigorous Exercise Can Cause Abnormal Pulmonary Function in Healthy Adolescents. Ann Am Thorac Soc 12:872-7
Schwindt, Christina D; Zaldivar, Frank; Eliakim, Alon et al. (2010) Inhaled fluticasone and the hormonal and inflammatory response to brief exercise. Med Sci Sports Exerc 42:1802-8
Schwindt, Christina D; Bacchus, Hyacinth; Leu, Szu-Yun et al. (2010) Characterization of the asthmatic population of St. Vincent and the Grenadines: asthma severity levels and atopic sensitization. J Asthma 47:871-7
Rosa, Jaime S; Schwindt, Christina D; Oliver, Stacy R et al. (2009) Exercise leukocyte profiles in healthy, type 1 diabetic, overweight, and asthmatic children. Pediatr Exerc Sci 21:19-33
Klebanova, Yana; Schwindt, Christina (2009) Infantile Systemic Hyalinosis: A Case Report of Compromised Cellular and Humoral Branches of the Immune System Leading to Infections. Pediatr Asthma Allergy Immunol 22:127-130
Schwindt, C D; Zaldivar, F; Wilson, L et al. (2007) Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma? Br J Sports Med 41:34-40
Shin, Hye-Won; Schwindt, Christina D; Aledia, Anna S et al. (2006) Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry. Am J Physiol Regul Integr Comp Physiol 291:R1741-8