Interactions of Diesel Exhaust and Respiratory Viruses in Asthmatic Children

柴油机尾气与哮喘儿童呼吸道病毒的相互作用

• 批准号: 8013076
• 负责人: TOBY C LEWIS
• 金额: $ 63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-13 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8013076
• 关键词: Acute; Adhesions; Affect; Air; Air Pollutants; Air Pollution; Animals; Asthma; Automobile Exhaust; Biological; Biological Markers; Budgets; Build-it; CXCL10 gene; Characteristics; Child; Child health care; Childhood Asthma; Clinical; Clinical Pathways; Cohort Studies; Complex; Diesel Exhaust; Disease; Distant; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemiologic Studies; Epidemiology; Epithelial Cells; Equation; Evaluation; Exhalation; Exposure to; Foundations; Free Radicals; Frequencies; Functional disorder; Funding; Health; Health Diary; Health Status; Home environment; IL8 gene; Incidence; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Interferons; Interleukin-8; Irrigation; Knowledge; Laboratories; Life; Linear Models; Liquid substance; Low Density Lipoprotein Receptor; Lower respiratory tract structure; Lung; Measures; Medical; Messenger RNA; Michigan; Modeling; Morbidity - disease rate; Nature; Nitric Oxide; Nitrogen Dioxide; Nose; Outcome; Outcome Measure; Oxidative Stress; Participant; Pathway interactions; Patient Self-Report; Pharmaceutical Preparations; Physiological; Policies; Pollution; Predisposition; Prospective Studies; Proteins; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; RANTES; Rattus; Recruitment Activity; Reporting; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Respiratory System; Respiratory Tract Infections; Respiratory physiology; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Robin bird; Role; Schools; Screening procedure; Severities; Specimen; Sulfur Dioxide; Symptoms; Testing; United States; Upper Respiratory Infections; Vehicle Emissions; Viral; Viral Load result; Virus; Virus Diseases; Virus Receptors; Visit; Wheezing; Work; airway hyperresponsiveness; airway inflammation; base; biological adaptation to stress; child trafficking; cohort; cost; cytokine; experience; falls; human TLR3 protein; improved; inflammatory marker; insight; isoprostaglandin F2alpha type-III; mRNA Expression; oxidant stress; particle; pollutant; prospective; protein expression; receptor; respiratory; respiratory virus; response; trafficking; urinary

DESCRIPTION (provided by applicant): Traffic-associated air pollution and respiratory viral infections (URIs) are well-documented, independent stimulants of asthma symptoms, and both are associated with significant asthma morbidity. There is growing laboratory and epidemiologic evidence to suggest that air pollution and URIs have interactive effects on the respiratory system. We have shown, in a prior epidemiologic study, that asthmatics with cold symptoms show more changes in lung function associated with prior exposure to high pollution than those without colds. However, the independent and interactive effects of pollutants attributable to diesel and other vehicular emissions and URIs on asthma exacerbation in children have not been extensively studied. We propose to test the general hypothesis that traffic-associated air pollution, specifically diesel exhaust, and respiratory viral infections combine to induce exaggerated airway responses in children with asthma. Two potential mechanisms of interaction will be evaluated: a) traffic-associated air pollution increases susceptibility to viral URI, and b) combined traffic pollutant exposure and URI elicits augmented inflammatory and oxidative stress responses leading to worse clinical asthma outcomes. To test this hypothesis of interaction, we propose these Specific Aims: 1. Compare asthmatic children living near highways with diesel truck traffic to those living distant from high volume roads for a) the frequency and characteristics of viral upper respiratory infections (URIs) and b) changes in nasal expression of viral adhesion proteins and interferons. 2. Prospectively evaluate the interactions between air pollution and viral upper respiratory infections on a) asthma morbidity, and b) markers of inflammation and oxidative stress. These hypotheses will be tested in a prospective study of a cohort of children with persistent asthma with extensively characterized exposure to diesel and other vehicular emissions. We will study the effects of diesel exhaust on incidence of viral infection and susceptibility to virus by evaluating nasal lavage specimens for viral infection, viral load, intercellular adhesion molecule (ICAM)-1, low-density lipoprotein receptor (LDL)-R, Toll-like receptor (TLR)-3, interferons (IFNs)-2, 3, and ; mRNA and protein expression using RT-PCR and ELISA, respectively. We will characterize interactive effects of diesel exhaust and PCR-confirmed viral infection on asthma health outcomes (primarily: fluctuations in daily measures of forced expiratory volume in 1 second (FEV1) and frequency of self-reported wheezing). We will also evaluate the role of enhanced inflammation and oxidative stress in these interactions by assessing markers of early physiologic response to exposures: exhaled nitric oxide (eNO), urinary 8-isoprostane, and nasal inflammatory cytokines (interleukin- 8/CXCL8, IP-10/CXCL10, RANTES/CCL5). The proposed studies will provide insight into the underlying biologic mechanisms and public health impacts of diesel-virus interactions in aggravation of childhood asthma. PUBLIC HEALTH RELEVANCE: This project will evaluate the impact on the health of asthmatic children of two very common "real world" asthma triggers: air pollution (especially diesel and vehicular exhaust) and respiratory viral infections. Enhanced knowledge of the extent and mechanisms of the interactions of these triggers will: a) give a more complete view of the public health impact of air pollution, facilitating scientifically-based air quality and traffic emissions policy; and b) enhance our understanding of the pathophysiology of asthma, a complex disease affecting 22.2 million people in the United States, thus pointing the way towards targeted therapies and public health approaches.

描述（由申请人提供）：与交通相关的空气污染和呼吸道病毒感染（URI）是有据可查的，具有哮喘症状的独立兴奋剂，并且两者都与明显的哮喘发病率有关。实验室和流行病学的证据表明空气污染和URI对呼吸系统具有互动效果。我们已经在先前的流行病学研究中表明，与没有感冒的哮喘患者相比，患有冷症状的哮喘患者显示出与先前暴露于高污染相关的肺功能变化。但是，尚未对柴油以及其他车辆排放的污染物的独立和互动作用对儿童哮喘恶化的污染物的影响尚未得到广泛研究。我们建议检验一个普遍的假设，即交通相关的空气污染，特别是柴油机排气和呼吸道病毒感染，以诱导哮喘儿童的夸张气道反应。将评估两种潜在的相互作用机制：a）与交通相关的空气污染增加了对病毒URI的敏感性，b）交通污染物的综合暴露和URI引发增加了炎症性和氧化应激反应，从而导致临床哮喘疼痛较差。为了检验这种相互作用的假设，我们提出了这些具体目的：1。将生活在柴油卡车交通的高速公路附近的哮喘儿童与远离大容量道路的生活方式相比，a）病毒上呼吸道感染（URI）和特征的频率和特征（uris）和B）在病毒粘附蛋白和干涉剂鼻粘附蛋白和干涉剂的鼻表达变化。 2。前瞻性评估空气污染与病毒上呼吸道感染在a）哮喘发病率上的相互作用，b）炎症和氧化应激的标志物。这些假设将在一项前瞻性研究中对一系列持续性哮喘的儿童进行检验，并具有广泛特征的柴油和其他车辆排放。我们将通过评估病毒感染，病毒载荷，细胞间粘附分子（ICAM）-1，低密度脂蛋白受体（LDL）-r，Toll-toll-toll-toll-like受体（TLR（TLR） - 3，Inters interserferns，Ifns Interfrefors-ifterns Interferns，我们将研究柴油排气对病毒感染发生率和病毒易感性的影响。 MRNA和蛋白质分别使用RT-PCR和ELISA。我们将表征柴油排气和PCR确认的病毒感染对哮喘健康结果的互动效果（主要是：每天在1秒（FEV1）（FEV1）和自我报告的喘​​息频率的每日量度的波动中发生波动）。我们还将通过评估对暴露的早期生理反应的标记来评估这些相互作用增强的炎症和氧化应激的作用：呼出的一氧化氮（ENO），尿液8-异丙烷和鼻炎性细胞因子（interleuukinkin- 8/cxcl8，ip-10/cxcl8，ip-10/cxcl10，rantess/ccl5）。拟议的研究将洞悉柴油 - 病毒相互作用对儿童哮喘的加剧的潜在生物学机制和公共卫生影响。公共卫生相关性：该项目将评估两个非常常见的“现实世界”哮喘触发因素的哮喘儿童的影响：空气污染（尤其是柴油和车辆排气）和呼吸道病毒感染。增强对相互作用程度和机制的知识 这些触发因素将：a）更完整地了解空气污染的公共卫生影响，促进 基于科学的空气质量和交通排放政策； b）增强我们对哮喘的病理生理学的理解，哮喘是一种复杂的疾病，影响了美国的2220万人，从而指出了针对性疗法和公共卫生方法的道路。