Chronic respiratory effects of early life PM exposure

生命早期接触 PM 的慢性呼吸系统影响

• 批准号: 7124234
• 负责人: KIRK R SMITH
• 金额: $ 59.46万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124234
• 关键词: Guatemala; air pollution; antioxidants; asthma; bronchodilators; child (0-11); child physical development; chronic disease /disorder; clinical research; early experience; energy source; environmental exposure; environmental health; enzyme activity; food processing /preparation; human subject; hypersensitivity; infant human (0-1 year); longitudinal human study; lung; particle; pollution related respiratory disorder; respiratory disorder epidemiology; respiratory function; sign /symptom

DESCRIPTION (provided by applicant): Accumulating evidence suggests that chronic exposure to particulate matter (PM) negatively affects growth of lung function in children and can lead to COPD in adults, but there is a dearth of information on the long-term effects of early life exposure to PM. In the proposed research we address the effects of exposure during infancy to biomass smoke PM on respiratory health later in childhood. Our mechanistic hypothesis is that the combustion-generated organic compounds present on fine particles in biomass smoke induce oxidative stress, upregulation of inflammatory cytokine production, and subsequent airway inflammation. Variation in the genotypes of key antioxidant enzymes (e.g., GSTM1 and GSTP1) may help to identify which children are more susceptible to the effects of inhaled PM on respiratory health. We propose to conduct a longitudinal follow-up study of a birth cohort of infants currently enrolled in a NIH-funded, randomized stove intervention trial to reduce acute lower respiratory illness (ALRI) in rural Guatemala. The improved cookstove markedly reduces biomass smoke exposure. After the participating child is 18 months old all families are offered the improved stove. Our proposed longitudinal follow-up study is designed to a) determine whether exposure to higher levels of PM during the first 18 months of life is associated with increased respiratory symptoms, bronchodilator responsiveness, sensitization to aeroallergens, and decreased rate of growth of lung function and somatic growth; and b) determine whether the GSTM1 null genotype renders children more susceptible and the GSTP1val105 variant less susceptible to the development of PM-induced oxidative stress and chronic respiratory effects. The effects of biomass smoke exposure have never been studied in a longitudinal design with quantitative exposure assessment. The current randomized intervention trial provides a unique opportunity to study the long-term effects of high exposure to biomass smoke/PM during the critical time window of lung development if follow-up is extended until later in childhood.

描述（由申请人提供）：越来越多的证据表明，长期接触颗粒物 (PM) 会对儿童肺功能的发育产生负面影响，并可能导致成人患慢性阻塞性肺病 (COPD)，但缺乏关于生命早期接触颗粒物 (PM) 的长期影响的信息。在拟议的研究中，我们探讨了婴儿期接触生物质烟雾 PM 对儿童后期呼吸系统健康的影响。我们的机制假设是，生物质烟雾中细颗粒上存在的燃烧产生的有机化合物会诱导氧化应激、炎症细胞因子产生的上调以及随后的气道炎症。关键抗氧化酶（例如 GSTM1 和 GSTP1）基因型的变异可能有助于确定哪些儿童更容易受到吸入 PM 对呼吸道健康的影响。我们建议对目前参加 NIH 资助的随机火炉干预试验的婴儿出生队列进行纵向随访研究，以减少危地马拉农村地区的急性下呼吸道疾病 (ALRI)。改进后的炉灶显着减少了生物质烟雾暴露。参与的孩子 18 个月大后，所有家庭都会获得改进的炉灶。我们提出的纵向随访研究旨在 a) 确定在生命的前 18 个月内暴露于较高水平的 PM 是否与呼吸道症状增加、支气管扩张反应性、对空气过敏原敏感以及肺功能和躯体生长速度降低有关； b) 确定 GSTM1 无效基因型是否使儿童更容易受到 PM 诱导的氧化应激和慢性呼吸系统影响的影响，而 GSTP1val105 变体是否更不易受到 PM 诱导的氧化应激和慢性呼吸系统影响的影响。生物质烟雾暴露的影响从未通过定量暴露评估的纵向设计进行过研究。目前的随机干预试验提供了一个独特的机会，可以研究在肺部发育的关键时间窗口内大量接触生物质烟雾/PM的长期影响，如果随访时间延长到儿童后期。