Diesel, Allergens and Gene Interaction and Child Atopy

描述（由研究者提供）：在生命早期暴露于细颗粒和超细颗粒，如柴油机排气颗粒（DEP）可能与呼吸系统疾病的后期发展相关。DEP可作为刺激物、用于将过敏原递送至气道的佐剂，并且可增强IgE介导的免疫应答。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研究，目前资助1）完成4岁以下儿童的临床检查，2）丰富DEP暴露的估计值。该补充为母研究增加了第三个具体目标，以确定高暴露于DEP是否与7岁时诊断为哮喘相关。儿童哮喘的诊断需要客观的措施，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，758名来自特应性家庭的婴儿从1岁起每年接受评估，3岁时的留存率为88%;目前正在进行4岁体检。儿童每年接受15种空气过敏原的皮肤点刺试验、DNA口腔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，包括5年来27个空气采样站的网络。源解析DEP签名方法和土地利用回归模型被用来估计一个孩子的早期生活和累积暴露于DEP。两个室内家庭灰尘样本评估了与狗、猫、蟑螂、尘螨以及内毒素和β-葡聚糖相关的过敏原水平。DEP暴露的定量估计与婴儿期和幼儿期的喘息显著相关。在GSTP 1等位基因和高DEP暴露之间发现了基因：环境相互作用，导致2岁时持续性喘息。其他最近的研究结果表明，在肺发育的关键窗口期间暴露于DEP，即，在出生后的前12个月，与3岁时慢性喘息增加2倍有关（aOR = 2.01 95%CI 1.02 - 4.31）。也有一个显着的相互作用与家庭暴露于内毒素（aOR=4.14 95% CI 1.5-11.7）。该补充将为我们提供第一次获得客观指标（eNO、鼻嗜酸性粒细胞、SPT、肺功能和MCCT）的机会，用于诊断7岁时的过敏性疾病。有了这些数据，我们将有哮喘的客观指标，并将能够对柴油和哮喘的相关性做出更明确的评估。公共卫生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研究，其目的是确定在生命早期暴露于DEP的儿童在儿童期发生过敏性疾病和哮喘的风险是否增加，以及这种风险是否受到遗传因素的影响。该研究目前获得资助，以完成对4岁以下儿童的临床检查，并确定参与研究的儿童暴露于DEP的情况。该补充增加了母研究的第三个具体目标，以确定高暴露于DEP是否与7岁时诊断为哮喘相关，使用客观措施，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。

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.