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: 7743092
• 负责人: CHRISTINA DANELL SCHWINDT
• 金额: $ 15.16万
• 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 2011-07-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743092
• 关键词: Abnormal Neutrophil; Acute; Adhesiveness; Advisory Committees; Affect; Air Pollutants; Air Pollution; Antioxidants; Arts; Asthma; Bronchoconstriction; CD11 Antigens; California; Cell Adhesion Molecules; Cells; Chemotaxis; Child; Childhood; Childhood Asthma; Clinical; Collaborations; Complement; Consumption; Data; Disease; Elastases; Environment; Epidemiology; Equilibrium; Exercise; Exercise Physiology; Exposure to; Flow Cytometry; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genomics; Glutathione Disulfide; Goals; Grant; Hypersensitivity skin testing; ICAM1 gene; IL8 gene; Immune; Immune Cell Activation; Immune response; Immune system; Immunologist; Immunology; Impairment; Incidence; Individual; Inflammation Mediators; Inflammatory Response; Interferons; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-4; Interleukin-5; Investigation; Island; Knowledge; Laboratories; Life; Linear Regressions; Link; Lymphocyte; Measurement; Measures; Mentors; Modeling; Molecular Biology; Morbidity - disease rate; NADPH Oxidase; National Institute of Environmental Health Sciences; Natural Immunity; Neutrophil Activation; Outcome; Oxidases; Oxidative Stress; Peroxidases; Pharmaceutical Preparations; Physicians; Physiological; Play; Pollution; Prevalence; Production; RANTES; Recording of previous events; Recruitment Activity; Research; Research Personnel; Research Project Grants; Role; SELL gene; Scheme; Schools; Scientist; Series; Severities; Severity of illness; Spirometry; Stimulus; Stress; Superoxides; Symptoms; Technology; Testing; Training Programs; Universities; Viral; Wheezing; acute stress; airborne allergen; asthmatic patient; atopy; base; biological adaptation to stress; career development; cohort; cytokine; diaries; experience; nephelometry; neutrophil; novel strategies; oxidation; pathogen; programs; release factor; response; skin hypersensitivity; statistics

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）： 这一申请在很大程度上是基于候选人先前在一个哮喘发病率迅速增加的发展中小岛国治疗哮喘儿童的经验。这一经历深深激励候选人获得深入的知识，既流行病学和病理生理学的儿童哮喘。候选人的目标是对这种新兴儿科疾病的机制进行独立调查。在加州大学欧文分校，候选人选择了两名医生科学家作为共同导师，他们的研究领域是：1）空气污染和儿童哮喘; 2）儿童对运动的免疫反应。这种合作的基本原理是，空气污染和运动都会加剧儿童哮喘，但这两种现象之间的联系机制尚不清楚。众所周知，即使在健康儿童中，运动也会导致先天免疫的强烈激活，中性粒细胞、中性粒细胞粘附分子和中性粒细胞氧化应激机制的增加，这些机制在支气管收缩中发挥作用。空气污染使中性粒细胞敏感，使它们更容易在环境因素（类似于运动）刺激先天免疫时释放这些因子。有趣的是，运动和污染也会影响淋巴细胞TH 1/TH 2极化，现在已知会影响中性粒细胞功能。尽管有这些令人信服的观察结果，但对哮喘儿童对运动的中性粒细胞反应或与淋巴细胞TH 1/TH 2平衡的关系知之甚少，这是拟议研究的重点。儿科哮喘研究的一个主要障碍是难以真实地描述疾病的严重程度。本研究旨在确定一组持续性哮喘儿童，在现场条件下使用散射比浊法和肺量测定法全面测量其临床严重程度和空气污染暴露，以研究新的疾病机制，使用基于实验室的精确控制的运动挑战，重点关注中性粒细胞功能和淋巴细胞TH 1/TH 2平衡。将从中性粒细胞基因组表达水平到中性粒细胞氧化应激反应的全身表现评估中性粒细胞功能。将通过细胞内细胞因子谱评估淋巴细胞TH 1/TH 2平衡。为了补充研究项目，候选人制定了一个强大的教学计划，包括统计学，分子生物学和流行病学的正式课程;以及正在进行的运动生理学和免疫学研究生研讨会系列。最后，候选人的职业发展将由项目共同导师和由免疫学家，运动生理学家和生物统计学家组成的杰出咨询委员会监督。

项目成果

Infantile Systemic Hyalinosis: A Case Report of Compromised Cellular and Humoral Branches of the Immune System Leading to Infections.

婴儿系统性玻璃样变：免疫系统细胞和体液分支受损导致感染的病例报告。

• DOI: 10.1089/pai.2009.0011
• 发表时间: 2009
• 期刊: Pediatric asthma, allergy & immunology
• 作者: Klebanova,Yana;Schwindt,Christina
• 通讯作者: Schwindt,Christina

Characterization of the asthmatic population of St. Vincent and the Grenadines: asthma severity levels and atopic sensitization.

圣文森特和格林纳丁斯哮喘人群的特征：哮喘严重程度和特应性致敏。

• DOI: 10.3109/02770903.2010.506682
• 发表时间: 2010
• 期刊: The Journal of asthma : official journal of the Association for the Care of Asthma
• 作者: Schwindt,ChristinaD;Bacchus,Hyacinth;Leu,Szu-Yun;Tjoa,Thomas;Klebanova,Yana;Delfino,RalphJ
• 通讯作者: Delfino,RalphJ