Environmental Influences on Perinatal Lung Development

环境对围产期肺部发育的影响

• 批准号: 6623324
• 负责人: KENT Ed PINKERTON
• 金额: $ 28.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623324
• 关键词: Macaca mulatta; behavioral /social science research tag; blood chemistry; environmental exposure; gel mobility shift assay; lung; lung development; neurotrophic factors; passive smoking; perinatal; polymerase chain reaction; postnatal growth disorder; pregnancy; respiratory function; respiratory hypersensitivity; tobacco abuse; ultrasonography; urinalysis

Childhood exposure to a variety of indoor air contaminants including environmental tobacco smoke (ETS) produces significant risks in asthma, airway hyperresponsiveness, and other respiratory symptoms such as cough, wheeze, and mucus production. Epidemiological studies suggest that exposure to ETS during the perinatal period may have adverse effects on lung function which can persist into adulthood. It has been estimated in the United States alone 200,000 to 1,000,000 children with asthma will have their condition worsened by exposure to ETS (USEPA, 1992). However, the mechanisms leading to this process are unknown. During the past 2.5 years, we have established a state-of-the-art inhalation system to study the effects of exposure to ETS on perinatal lung development in a nonhuman primate, the Rhesus macaque monkey. Exposure to ETS has been done using aged and diluted sidestream cigarette smoke as a surrogate for ETS. Two chambers located at the California Regional Primate Research Center Inhalation Facility have been expressly designed and configured to create conditions for passive smoke exposure to monkeys during pregnancy and early postnatal development under carefully controlled conditions. These studies have demonstrated significant alterations in lung development following exposure to ETS. These effects include changes in immune effector and inflammatory cells in the lung air spaces, alterations in pulmonary and peripheral blood cytokines and neurotrophins, alterations in the innervation and epithelial composition of the trachea, and changes in the activity and distribution of pulmonary cytochrome P450 monooxygenases and glutathione-S-transferases. All these changes are evident by 2.5 months of age in infant Rhesus monkeys. These findings confirm that ETS exposure during perinatal development significantly affects the lungs of non-human primate infants. We hypothesize that these changes represent the initial steps in the genesis of an asthmatic-like condition solely due to perinatal exposure to ETS. We also hypothesize that critical windows of exposure are present during the perinatal period which will exacerbate this effect. We propose to test these hypotheses by continuing to study this model in the Rhesus monkey to (1) determine the effects of exposure to ETS during specific periods of perinatal development in monkeys from early gestation to 6 months postnatal age using physiologic, biochemical and anatomical measures and (2) determine if cessation of exposure to ETS following 6 months postnatal age will still be associated with persistent changes in the respiratory system. Such studies should help us to better understand the potential mechanisms by which fetal and early postnatal exposure to environmental contaminants could lead to lasting, adverse consequences in children.

儿童时期接触各种室内空气污染物，包括环境烟草烟雾 (ETS)，会导致哮喘、气道高反应性和其他呼吸道症状（例如咳嗽、喘息和粘液产生）的重大风险。 流行病学研究表明，围产期接触 ETS 可能会对肺功能产生不利影响，这种影响可能持续到成年期。 据估计，仅在美国就有 200,000 至 1,000,000 名哮喘儿童因接触 ETS 而病情恶化（USEPA，1992）。 然而，导致这一过程的机制尚不清楚。 在过去 2.5 年中，我们建立了最先进的吸入系统，以研究接触 ETS 对非人类灵长类动物（恒河猴）围产期肺部发育的影响。 使用老化和稀释的侧流香烟烟雾作为 ETS 的替代物来进行 ETS 暴露。 位于加州地区灵长类动物研究中心吸入设施的两个房间经过专门设计和配置，旨在为猴子在怀孕期间和产后早期发育期间在严格控制的条件下被动接触烟雾创造条件。这些研究表明，接触 ETS 后肺部发育发生显着变化。 这些影响包括肺气腔中免疫效应器和炎症细胞的变化、肺和外周血细胞因子和神经营养因子的变化、气管神经支配和上皮组成的变化以及肺细胞色素P450单加氧酶和肺细胞色素P450单加氧酶的活性和分布的变化。谷胱甘肽-S-转移酶。 所有这些变化在恒河猴幼年 2.5 个月大时就变得很明显。 这些发现证实，围产期发育期间的 ETS 暴露显着影响非人类灵长类婴儿的肺部。 我们假设这些变化代表了仅由于围产期接触 ETS 导致的哮喘样病症发生的初始步骤。 我们还假设围产期存在关键的暴露窗口，这将加剧这种影响。 我们建议通过继续在恒河猴中研究该模型来检验这些假设，以（1）使用生理、生化和解剖学措施确定猴子从妊娠早期到产后 6 个月的围产期发育特定时期暴露于 ETS 的影响(2) 确定产后 6 个月后停止接触 ETS 是否仍与呼吸系统的持续变化相关。 此类研究应有助于我们更好地了解胎儿和产后早期接触环境污染物可能导致儿童持久不良后果的潜在机制。