Pulmonary effects of biomass fuel indoor PM from rural India

印度农村生物质燃料室内 PM 对肺部的影响

• 批准号: 8459425
• 负责人: Shyam Biswal
• 金额: $ 5.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-10 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459425
• 关键词: A/J Mouse; Aerosols; Affect; Air; Antioxidants; Asthma; Attenuated; Award; Bacteria; Biological; Biomass; Broccoli - dietary; Bronchoalveolar Lavage; Cattle; Cells; Chemicals; Chemoprotection; Chest; Child; Childhood Asthma; Chronic Obstructive Airway Disease; Collection; Data; Diet; Dietary Intervention; Dietary Supplementation; Endotoxins; Environment; Environmental Tobacco Smoke; Exposure to; Foundations; Funding; Future; Genetic; Goals; Grant; Home environment; Household; Housing; Immune; Immune response; India; Inflammation; Inflammatory; Inhalation Exposure; Intervention; Lead; Link; Lung; Lung diseases; Measures; Metals; Modeling; Mus; Outcome Study; Oxidative Stress; Ozone; Particulate Matter; Pathway interactions; Phagocytosis; Pneumonia; Population; Prevention Research; Proteins; Regulation; Relative (related person); Research; Research Personnel; Respiratory Tract Infections; Risk Factors; Rural; Rural Population; Sampling; Smoke; Source; Sulforaphane; TNFRSF5 gene; Testing; Tobacco; Toxic effect; United States National Institutes of Health; Urban Population; Wood material; airway hyperresponsiveness; ambient particle; chemokine; cohort; cooking; cytokine; disorder prevention; innate immune function; macrophage; mouse development; mouse model; non-smoker; novel strategies; particle; particle exposure; programs; response

Project Summary About 3 billion people, half the worldwide population, are exposed to smoke from biomass fuel compared with 1 billion people who smoke tobacco, which suggests that exposure to biomass smoke might be the biggest risk factor for respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and respiratory infections globally. There is a disproportionate increase in COPD and asthma among non-smokers in rural India who use biomass for cooking. Ambient air particulate matter (PM) is well studied and linked to increased pulmonary oxidative stress and inflammation and causes greater respiratory diseases in the urban population; however, the effects of indoor PM due to biomass fuel on lungs and innate immune defense in the rural population remains unclear. The PI and co-investigators from JHU are collaborating with the two key pulmonologists from the India team who have established a rural cohort in Vadu village of Pune district (Maharashtra, India) that uses biomass fuel as their sole source of cooking fuel with high indoor PM. The PIs have collected indoor air PM (from rural houses with non-smokers). The main goal of this proposal is to characterize and compare the indoor PM from various biomass sources (cow dung, wood, and crop residue), and perform controlled mouse model studies using indoor PM to dissect the effects on lungs and innate immune response without the confounding effects of ozone and other gaseous components. The outcome from this study will help to develop future strategies for intervention in the rural population to reduce lung diseases. This proposal is an extension of the recently awarded FIRCA Eligible Award "Children's Environmental and Disease Prevention Research Center" P01 ES018176-01 (Project 3, 9/1/2009 - 8/31/2014). Project 3 (Mechanisms of asthma-dietary interventions against environmental triggers) and will test the hypothesis that antioxidants such as sulforaphane present in the diet can cause chemoprotection by activating the Nrf2 pathway to counteract oxidative stress and inflammation and protect against the pulmonary asthmatic response following ambient air particle exposure in mice. The specific aims in our current proposal provide a unique opportunity to test our hypothesis and to study the biological effects of indoor PM due to exposure to biomass fuel: SA1: To collect indoor PM and determine physicochemical characterization of different sources of biomass collected in rural homes. Homes in rural India use either cow dung, wood, crop residue, or a combination of the three for cooking. We have identified homes that will use only one biomass fuel source. The size and concentration of indoor PM in rural homes that use these different sources of biomass are being collected, and we will determine protein, endotoxin, metal and organic concentration in these indoor PM samples. This data will be helpful for characterizing the relative toxicity of each fuel source. SA2: To compare the effects of various sources of biomass-derived indoor PM collected in rural homes on lungs and innate immune response. We will test the hypothesis that indoor PM causes (a) oxidative stress, inflammation, and airway hyper-reactivity, and (b) inhibits the innate immune response. We will perform pulmonary aspiration of different indoor PM samples in A/J mice and measure markers of oxidative stress, inflammatory cells in bronchoalveolar lavage and lungs, cytokines and chemokines, and airway hyper- reactivity. We will also determine whether exposure of macrophages to indoor PM suppresses phagocytosis of bacteria. Although an inhalation exposure model is more realistic, airway instillation has been demonstrated to be a very effective model for comparing relative toxicity in mice where samples are limited. A/J mice were chosen because of their heightened sensitivity to airway challenges.

项目摘要 大约30亿人口（全球人口一半）与生物质燃料相比暴露于 吸烟烟草的10亿人表明，暴露于生物质烟雾可能是最大的风险 呼吸道疾病的因素，例如慢性阻塞性肺疾病（COPD），哮喘和呼吸道 全球感染。农村的非吸烟者中的COPD和哮喘的增加不成比例 印度使用生物质进行烹饪。环境空气颗粒物（PM）进行了充分的研究，并与增加有关 肺氧化应激和炎症，并导致城市人口更大的呼吸道疾病； 但是，由于生物质燃料对肺部和农村的先天免疫防御引起的室内PM的影响 人口尚不清楚。 JHU的PI和共同投资者正在与这两个密钥合作 来自印度团队的肺科医生在浦那区瓦杜村建立了一个农村队列 （印度马哈拉施特拉邦）使用生物质燃料作为高室内PM的唯一烹饪燃料来源。 pis 已经收集了室内空气PM（来自非吸烟者的农村房屋）。该提议的主要目标是 表征和比较来自各种生物质源（牛粪，木材和作物残留物）的室内PM， 并使用室内PM进行受控的小鼠模型研究，以剖析对肺和先天性的影响 免疫反应没有臭氧和其他气体成分的混杂作用。结果 这项研究将有助于制定未来的干预策略，以减少肺部疾病。 该提案是最近授予的FIRCA奖项的“儿童环境和 疾病预防研究中心“ P01 ES018176-01（项目3，9/1/2009-8/31/2014）。项目3 （针对环境触发器的哮喘 - 侵犯干预措施的机制），并将检验以下假设。 饮食中存在的抗氧化剂（例如硫烷）可以通过激活NRF2引起化学保护 抵消氧化应激和炎症的途径，并预防肺部哮喘 小鼠环境空气颗粒暴露后的反应。我们当前建议中的具体目的提供了 由于暴露于 生物质燃料：SA1：收集室内PM并确定不同的物理化学表征 在农村房屋中收集的生物质来源。印度农村的房屋使用牛粪，木材，农作物 残留物，或三个用于烹饪的组合。我们已经确定了只使用一个生物量的房屋 燃料来源。使用这些不同来源的农村房屋中室内PM的大小和浓度 正在收集生物量，我们将确定蛋白质，内毒素，金属和有机浓度 这些室内PM样品。这些数据将有助于表征每个燃料源的相对毒性。 SA2：比较在农村房屋中收集的生物质衍生室内PM的各种源的影响 关于肺部和先天免疫反应。我们将测试室内PM引起的假设（a）氧化 应力，炎症和气道高反应性，（b）抑制先天免疫反应。我们将表演 A/J小鼠中不同室内PM样品的肺抽吸，并测量氧化应激的标志物， 支气管肺泡灌洗和肺，细胞因子和趋化因子以及气道高 - 反应性。我们还将确定巨噬细胞暴露于室内PM是否抑制了吞噬作用 细菌。尽管吸入暴露模型更现实，但气道滴注已被证明 成为一个非常有效的模型，用于比较样品有限的小鼠相对毒性。 A/J鼠是 之所以选择他们对气道挑战的敏感性。