Effects of Early Life Exposure to Household Air Pollution on DNA Methylation and Respiratory Disease in Guatemalan Children from the Household Air Pollution Intervention Network (HAPIN) Trial

根据家庭空气污染干预网络 (HAPIN) 试验，生命早期接触家庭空气污染对危地马拉儿童 DNA 甲基化和呼吸道疾病的影响

• 批准号: 10660568
• 负责人: John Patrick Mccracken
• 金额: $ 67.64万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660568
• 关键词: 1 year old; 2 year old; 3 year old; 7 year old; Address; Adopted; Adult; Age; Air Pollution; Animals; Area; Biogenesis; Biological; Biological Markers; Blood; Carbon Black; Cessation of life; Charcoal; Child; Childhood; Chronic; Chronic Disease; Coal; DNA Methylation; Detection; Development; Dryness; Effectiveness; Energy-Generating Resources; Epidemiology; Epigenetic Process; Exposure to; Funding; Gases; Growth; Guatemala; Guatemalan; Health; Heterogeneity; Hospitals; Household; Household Air Pollution; Incidence; Infant; Intervention; Intervention Trial; Life; Lung; Measures; Molecular; Observational Study; Oxygen; Participant; Pattern; Persons; Petroleum; Pneumonia; Policies; Population; Predisposition; Pregnancy; Randomized; Research; Research Design; Respiratory Disease; Risk; Risk Assessment; Rural; Severities; Source; Spirometry; Spottings; Techniques; Time; Visit; Wood material; Work; ambient air pollution; attributable mortality; burden of illness; clinical diagnosis; cohort; cooking; disease diagnosis; disorder prevention; early childhood; early life exposure; environmental tobacco smoke; epigenetic marker; fine particles; follow-up; health data; improved; infancy; insight; intervention effect; low and middle-income countries; low income country; lung development; methylation biomarker; methylation pattern; post intervention; premature; prenatal; prenatal exposure; pulmonary function; respiratory; respiratory health; response; solid fuel; tool; ultrasound; 1 year old; 2 year old; 3 year old; 7 year old; Address; Adopted; Adult; Age; Air Pollution; Animals; Area; Biogenesis; Biological; Biological Markers; Blood; Carbon Black; Cessation of life; Charcoal; Child; Childhood; Chronic; Chronic Disease; Coal; DNA Methylation; Detection; Development; Dryness; Effectiveness; Energy-Generating Resources; Epidemiology; Epigenetic Process; Exposure to; Funding; Gases; Growth; Guatemala; Guatemalan; Health; Heterogeneity; Hospitals; Household; Household Air Pollution; Incidence; Infant; Intervention; Intervention Trial; Life; Lung; Measures; Molecular; Observational Study; Oxygen; Participant; Pattern; Persons; Petroleum; Pneumonia; Policies; Population; Predisposition; Pregnancy; Randomized; Research; Research Design; Respiratory Disease; Risk; Risk Assessment; Rural; Severities; Source; Spirometry; Spottings; Techniques; Time; Visit; Wood material; Work; ambient air pollution; attributable mortality; burden of illness; clinical diagnosis; cohort; cooking; disease diagnosis; disorder prevention; early childhood; early life exposure; environmental tobacco smoke; epigenetic marker; fine particles; follow-up; health data; improved; infancy; insight; intervention effect; low and middle-income countries; low income country; lung development; methylation biomarker; methylation pattern; post intervention; premature; prenatal; prenatal exposure; pulmonary function; respiratory; respiratory health; response; solid fuel; tool; ultrasound

PROJECT SUMMARY Household air pollution (HAP) from solid fuel use causes an estimated 400,000 chronic obstructive pulmonary (COPD) deaths each year. Although lung function and lower respiratory disease in childhood are determinants of COPD risk later in life, there are few studies of the influence of early life HAP exposure on respiratory health later in childhood. We propose a HAP study design that is sensitive to emerging chronic respiratory effects by incorporating three key features: 1) assessment of exposure during early life windows of susceptibility, 2) a strong exposure contrast introduced by a randomized intervention, and 3) sensitive endpoints that predict chronic disease later in life. Gestation and infancy are critical windows of susceptibility due to the rapid lung development. Previous HAP intervention trials had only low to moderate effectiveness for reducing HAP exposure. The Household Air Pollution Intervention Network (HAPIN) trial (2017-2021) offers a time-sensitive, unique research opportunity because the liquefied petroleum gas (LPG) stove and fuel intervention lowered median gestational fine particulate matter (PM2.5) exposure in Guatemalan participants by 77%, from 98 to 23 µg/m3. The intervention continued until age 1 year and extensive health data were collected, including pneumonia incidence and severity. We have maintained follow-up of the cohort post-intervention, assessing HAP exposure and child growth at age 2 years plus lung function at age 3 years. We posit that childhood lung function and lower respiratory disease episodes are sensitive indicators of HAP health effects that relate to adulthood COPD. DNA methylation (DNAm) and pneumonia during infancy may influence these respiratory endpoints later in childhood. We propose to leverage our successful LPG cooking intervention in Guatemala to investigate effects of early life HAP exposure on longer-term respiratory health and explore DNAm as a biomarker. We hypothesize that the randomized LPG cooking intervention and lower PM2.5 and black carbon (BC) exposure will be associated with DNAm at age 1 year and greater lung function and fewer lower respiratory disease episodes at age 4-7 years. Aim 1. Estimate effects of a randomized LPG cooking intervention during gestation and infancy (age <1 year) (Aim 1.A) and HAP exposure (PM2.5 and BC) during and after the intervention (Aim1.B) on lung function trajectories (age 3-7 years) and lower respiratory disease incidence (ages of 4 to 7 years). Aim 2. Estimate effects of a randomized LPG cooking intervention (Aim 2.A) and HAP exposure (Aim 2.B) during gestation and early infancy (age <1 year) on DNAm biomarkers at the end of the intervention period (age 1 year). Aim 3. Determine whether DNAm at age 1 year (Aim3.A) and pneumonia episodes until age 1 year (Aim 3.B) are associated with lung function trajectories and lower respiratory disease incidence between ages of 3 to 7 years. Effects of early life HAP on lung function and lower respiratory disease later in childhood would have important implications for the early life origins of COPD in populations exposed to HAP, and identifying epigenetic changes that might underpin this relationship could lead to improved research and interventions.

项目摘要 固体燃料使用的家庭空气污染（HAP）导致估计40万慢性阻塞性肺 （COPD）每年死亡。尽管儿童期肺功能和下呼吸道疾病是确定的 COPD在以后的生命后期风险，很少有关于早期HAP暴露对呼吸健康的影响的研究 在童年时期。我们提出了一种HAP研究设计，该设计对新兴的慢性呼吸作用敏感 合并三个关键特征：1）评估易感性早期窗户期间暴露的评估，2）强大 由随机干预引入的暴露对比和3）预测慢性的敏感终点 疾病以后的生活。妊娠和婴儿期是由于肺部快速发育而导致敏感性的关键窗口。 以前的HAP干预试验仅具有低至中等的有效性来减少HAP暴露。这 家庭空气污染干预网络（HAPIN）试验（2017-2021）提供了时间敏感的独特研究 机会是因为液化石油气（LPG）炉灶和燃料干预降低了妊娠中位数 危地马拉参与者的细颗粒物（PM2.5）暴露于98至23 µg/m3的77％。干预 持续到1岁，并收集了广泛的健康数据，包括肺炎事件和严重程度。 我们已经维持了干预后队列的随访，评估了2岁时的HAP暴露和儿童成长 年龄加上3岁的肺功能。我们指出童年肺功能和下呼吸道疾病 发作是与成年COPD有关的HAP健康效应的敏感指标。 DNA甲基化（DNAM） 婴儿期间的肺炎可能会影响童年后期的这些呼吸道终点。我们建议 利用我们在危地马拉成功成功的液化石油气烹饪干预来研究早期生命的影响 关于长期呼吸健康，并将DNAM作为生物标志物探索。我们假设随机LPG 烹饪干预和较低的PM2.5和黑色碳（BC）的暴露将与1岁的DNA相关 4-7岁时，肺功能更大，下呼吸道疾病发作更少。目标1。估计效应 妊娠和婴儿期间的随机LPG烹饪干预（年龄<1年）（AIM 1.A）和HAP 干预期间和之后的暴露（PM2.5和BC）（AIM1.B）肺功能轨迹（年龄3-7岁） 和下呼吸道疾病事件（4至7岁年龄）。 AIM 2。估计随机LPG的效果 烹饪干预（AIM 2.A）和HAP暴露（AIM 2.B）在妊娠和婴儿期（年龄<1岁） 在干预期结束时（1岁）结束时DNAM生物标志物。目标3。确定DNAN年龄是否 1年（AIM3.A）和肺炎发作至1岁（AIM 3.B）与肺功能有关 3至7岁之间的轨迹和下呼吸道疾病。早期生命的影响对 儿童晚期肺功能和下呼吸道疾病将对早期产生重要影响 COPD的起源在暴露于HAP的人群中，并确定可能支持这一点的表观遗传变化 关系可能导致改进的研究和干预措施。