Diesel, Allergens and Gene Interaction and Child Atopy

柴油、过敏原和基因相互作用以及儿童特应性

基本信息

批准号：
7528456
负责人：
Grace LeMasters
金额：
$ 46.46万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7528456
关键词：
7 year old Address Adjuvant Adverse effects African American Aftercare Age Air Pollution Albuterol Alleles Allergens Allergic Allergic rhinitis Animals Area Asthma Atopic Dermatitis Autopsy Biological Markers Birth Breathing Bronchial Provocation Tests Bronchodilator Agents CD14 gene Canis familiaris Carbon Child Childhood Childhood Asthma Chronic Cities Clinic Visits Clinical Cohort Studies Condition Cotinine DNA Data Deposition Development Diagnosis Dictyoptera Diesel Exhaust Disease Disease regression Dust Endotoxins Enrollment Ensure Environment Environmental Exposure Environmental Risk Factor Environmental Tobacco Smoke Epithelial Cells Exclusion Exhalation Exposure to Extrinsic asthma Family Felis catus Female Figs - dietary Funding Future GSTP1 gene Gases Gender Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Transcription Genetic Variation Genotype Glucans Glutathione S-Transferase Grant Hair Health Home environment House Dust Mite Allergens Human Hypersensitivity IL4 gene IgE Immune response Immunity Incidence Infant Inflammation Inflammatory Interleukin-13 Interleukin-4 Investigation Irritants Journals Knowledge Lead Life Lung Lung diseases Measurement Measures Mediating Methodology Methods Metric Mexico Modeling Molds Monitor Morbidity - disease rate Morus Nicotine Nitric Oxide Nose Other Genetics Outcome Oxidative Stress Parents Particulate Pattern Peer Review Peripheral Phenotype Policies Pollen Polymorphism Analysis Pre-Post Tests Predisposition Progress Reports Public Health Pulmonary Function Test/Forced Expiratory Volume 1 Pulmonary function tests Purpose Pyrenes Rate Reactive Oxygen Species Relative (related person)Research Personnel Respiration Disorders Respiratory physiology Rhinitis Risk Risk Factors Role Sampling Severities Skin Source Spirometry Surface Symptoms T-Lymphocyte Testing Time Ultrafine United States Environmental Protection Agency Variant Wheezing Woman Work air monitoring air sampling airborne allergen airway epithelium airway inflammation airway obstruction atopy beta-Glucans cohort cytochrome P-450 CYP2A6 (human)day disease natural history early childhood environmental allergen eosinophil exhaust forging gene environment interaction gene interaction genetic variant glutathione S-transferase pi improved inclusion criteria infancy journal article land use lung development macrophage member methacholine mortality non-smoker parent grant particle particle exposure postnatal promoter prospective pyrene pyroglyphid research clinical testing respiratory response time interval trafficking

项目摘要

DESCRIPTION (provided by investigator): Exposure to fine and ultra fine particles such as diesel exhaust particles (DEP) during early life may be associated with the later development of respiratory disorders. DEP may act as an irritant, an adjuvant for delivery of allergens to the airway and may potentiate an IgE mediated immune response. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort currently funded to 1) complete clinical examinations of children through age four and 2) enrich the estimates of exposure to DEP. This supplement adds a third specific aim to the parent study to determine if high exposure to DEP is associated with a diagnosis of asthma at age 7. Diagnosis of asthma in children requires objective measures, including pulmonary function testing, markers of airway inflammation (eNO), and methacholine challenge testing. To date, 758 infants from atopic families were evaluated annually from age 1, with an 88 per cent retention rate through age 3; age 4 physical exams are currently underway. Children have received annual skin prick tests for 15 aeroallergens, DNA buccal samples and yearly hair samples for assessing nicotine and cotinine levels. CCAAPS has extensive PM2.5 data that includes a network of 27 air sampling stations over 5 years. Source apportionment DEP signature methodologies and a land use regression model were used to estimate a child's early life and cumulative exposure to DEP. Two indoor home dust samples evaluated levels of allergens associated with dog, cat, cockroach, dust mite, as well as endotoxin, and beta-glucan. Quantitative estimates of DEP exposure was significantly associated with wheezing during infancy and early childhood. A gene:environment interaction was found between alleles of GSTP1 and high DEP exposure resulting in persistent wheeze at age two. Other recent findings indicate that exposure to DEP during a critical window of lung development, i.e., the first 12 months of life, is associated with a two fold increase in chronic wheezing at age 3 (aOR = 2.01 95 per cent CI 1.02 - 4.31). There also was a significant interaction with home exposure to endotoxin (aOR=4.14 95 per cent CI 1.5-11.7). This supplement will provide our first opportunity to obtain objective measures (eNO, nasal eosinophils, SPT, lung function, and MCCT) for the diagnosis of allergic diseases at age 7. With these data, we will have objective measures of asthma and will be able to make a more definitive assessment of an exposure-response relationship related to diesel and asthma. PUBLIC HEALTH RELEVANCE The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort whose purpose is to determine if children exposed to DEP early in life are at increased risk for the development of allergic disease and asthma during childhood and if this risk is modified by genetic factors. The study is currently funded to complete clinical examinations of children through age four and determine the exposure to DEP of children enrolled in the study. This supplement adds a third specific aim to the parent study to determine if high exposure to DEP is associated with a diagnosis of asthma at age 7 using objective measures including pulmonary function testing, markers of airway inflammation (eNO), and methacholine challenge testing.

描述（由研究者提供）：生命早期接触细颗粒和超细颗粒，如柴油机尾气颗粒 (DEP) 可能与后来出现呼吸系统疾病有关。 DEP 可作为刺激剂、将过敏原输送至气道的佐剂，并可增强 IgE 介导的免疫反应。辛辛那提儿童过敏和空气污染研究 (CCAAPS) 是一项前瞻性出生队列，目前资助的目的是 1) 对 4 岁以下儿童完成临床检查，2) 丰富 DEP 暴露的估计。该补充品为母研究增加了第三个具体目标，即确定高浓度 DEP 暴露是否与 7 岁时诊断出哮喘有关。儿童哮喘的诊断需要客观措施，包括肺功能测试、气道炎症标志物 (eNO)和乙酰甲胆碱激发试验。迄今为止，每年有 758 名来自特应性家庭的婴儿从 1 岁开始接受评估，到 3 岁的保留率为 88%； 4 岁体检目前正在进行中。儿童每年接受 15 种空气过敏原的皮肤点刺测试、口腔 DNA 样本和每年的头发样本，以评估尼古丁和可替宁水平。 CCAAPS 拥有广泛的 PM2.5 数据，其中包括 5 年来由 27 个空气采样站组成的网络。使用源解析 DEP 特征方法和土地利用回归模型来估计儿童的早期生活和 DEP 的累积暴露。两个室内家庭灰尘样本评估了与狗、猫、蟑螂、尘螨相关的过敏原以及内毒素和 β-葡聚糖的水平。 DEP 暴露的定量估计与婴儿期和幼儿期的喘息显着相关。在 GSTP1 等位基因和高 DEP 暴露之间发现了基因：环境相互作用，导致两岁时出现持续性喘息。最近的其他研究结果表明，在肺部发育的关键时期（即生命的前 12 个月）接触 DEP 与 3 岁时慢性喘息增加两倍相关（aOR = 2.01 95% CI 1.02 - 4.31）。家庭接触内毒素也存在显着的相互作用（aOR=4.14 95% CI 1.5-11.7）。该补充品将为我们提供第一次机会获得客观测量值（eNO、鼻嗜酸性粒细胞、SPT、肺功能和 MCCT），以诊断 7 岁时过敏性疾病。有了这些数据，我们将能够对哮喘进行客观测量对与柴油和哮喘相关的暴露-反应关系进行更明确的评估。公共健康相关性辛辛那提儿童过敏和空气污染研究 (CCAAPS) 是一项前瞻性出生队列，其目的是确定生命早期接触 DEP 的儿童在儿童时期患过敏性疾病和哮喘的风险是否增加，以及这种风险是否会增加是被遗传因素改变的。该研究目前获得资助，用于完成四岁以下儿童的临床检查，并确定参与研究的儿童接触 DEP 的情况。该补充在母研究的基础上增加了第三个具体目标，即使用肺功能测试、气道炎症标志物 (eNO) 和乙酰甲胆碱激发测试等客观措施来确定高暴露 DEP 是否与 7 岁时诊断出哮喘相关。