Exercise, Pollution, and Neutrophils in Pediatric Asthma

运动、污染和中性粒细胞与小儿哮喘的关系

• 批准号: 7036951
• 负责人: CHRISTINA DANELL SCHWINDT
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036951
• 关键词: T lymphocyte; air pollution; asthma; atopy; blood chemistry; cardiovascular stress test; cell adhesion; chemotaxis; children; clinical research; cytokine; environmental exposure; exercise; exercise tolerance; field study; gene expression profiling; human subject; immune response; interferons; microarray technology; nephelometry; neutrophil; oxidative stress; patient oriented research; respiratory disorder epidemiology; spirometry

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：