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: 8210689
• 负责人: Shyam Biswal
• 金额: $ 6.61万
• 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/8210689
• 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

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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. These studies will determine how indoor particulate matter present in polluted air of homes that use biomass for cooking affect lungs and immune defense and develop a novel strategy to counteract their deleterious effects.

描述（由申请人提供）：约 30 亿人（占全球人口的一半）接触生物质燃料产生的烟雾，而吸烟者有 10 亿人，这表明接触生物质烟雾可能是全球呼吸系统疾病（如慢性阻塞性肺病 (COPD)、哮喘和呼吸道感染）的最大风险因素。在印度农村使用生物质做饭的非吸烟者中，慢性阻塞性肺病和哮喘的发病率不成比例地增加。环境空气颗粒物 (PM) 已得到充分研究，表明与肺部氧化应激和炎症增加有关，并导致城市人口出现更严重的呼吸道疾病；然而，生物质燃料引起的室内 PM 对农村人口肺部和先天免疫防御的影响仍不清楚。来自 JHU 的 PI 和联合研究人员正在与印度团队的两位主要肺病学家合作，他们在浦那区（印度马哈拉施特拉邦）瓦杜村建立了一个农村队列，该队列使用生物质燃料作为室内 PM 较高的烹饪燃料的唯一来源。 PI 收集了室内空气 PM（来自不吸烟的农村房屋）。该提案的主要目标是表征和比较来自各种生物质来源（牛粪、木材和作物残渣）的室内 PM，并使用室内 PM 进行受控小鼠模型研究，以剖析对肺部和先天免疫反应的影响，而不考虑臭氧和其他气体成分的混杂影响。这项研究的结果将有助于制定未来干预农村人口以减少肺部疾病的策略。该提案是最近授予的 FIRCA 合格奖“儿童环境与疾病预防研究中心”P01 ES018176-01（项目 3，2009 年 9 月 1 日 - 2014 年 8 月 31 日）的延伸。项目 3（针对环境触发因素的哮喘饮食干预机制）将测试以下假设：饮食中存在的抗氧化剂（例如萝卜硫素）可以通过激活 Nrf2 通路来产生化学保护作用，从而对抗氧化应激和炎症，并防止小鼠暴露于环境空气颗粒后出现肺部哮喘反应。我们当前提案中的具体目标提供了一个独特的机会来检验我们的假设并研究由于暴露于生物质燃料而导致的室内 PM 的生物效应： SA1：收集室内 PM 并确定在农村家庭中收集的不同来源的生物质的物理化学特征。印度农村的家庭使用牛粪、木材、农作物残渣或三者的组合来做饭。我们已经确定了仅使用一种生物质燃料来源的家庭。正在收集使用这些不同生物质来源的农村家庭的室内 PM 的大小和浓度，我们将确定这些室内 PM 样本中的蛋白质、内毒素、金属和有机物浓度。该数据将有助于表征每种燃料来源的相对毒性。 SA2：比较农村家庭收集的各种生物质来源的室内 PM 对肺部和先天免疫反应的影响。我们将检验以下假设：室内 PM 会导致 (a) 氧化应激、炎症和气道高反应性，以及 (b) 抑制先天免疫反应。我们将对 A/J 小鼠的不同室内 PM 样本进行肺部抽吸，并测量氧化应激标记物、支气管肺泡灌洗液和肺部的炎症细胞、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 是否会抑制细菌的吞噬作用。尽管吸入暴露模型更为现实，但气道滴注已被证明是在样本有限的情况下比较小鼠相对毒性的非常有效的模型。选择 A/J 小鼠是因为它们对气道挑战高度敏感。 公共卫生相关性：约 30 亿人（占全球人口的一半）接触生物质燃料烟雾，而吸烟者有 10 亿人，这表明接触生物质烟雾可能是全球慢性阻塞性肺病 (COPD)、哮喘和呼吸道感染等呼吸系统疾病的最大风险因素。这些研究将确定使用生物质烹饪的家庭污染空气中存在的室内颗粒物如何影响肺部和免疫防御，并制定一种新的策略来抵消其有害影响。