Pulmonary effects of biomass fuel indoor PM from rural India

项目摘要 大约30亿人，占世界人口的一半，暴露在生物质燃料产生的烟雾中，而 10亿人吸烟，这表明暴露在生物质烟雾中可能是最大的风险 呼吸系统疾病的因素，如慢性阻塞性肺疾病(COPD)、哮喘和呼吸系统疾病 全球感染。在农村不吸烟的人中，慢性阻塞性肺病和哮喘的发病率增加不成比例。 印度人用生物质做饭。环境空气颗粒物(PM)被充分研究，并与增加的 肺部氧化应激和炎症，并在城市人口中引起更严重的呼吸系统疾病； 然而，生物质燃料引起的室内PM对农村人的肺部和天然免疫防御的影响 人口仍不清楚。PI和JHU的联合调查员正在与这两个关键人物合作 来自印度团队的肺病学家，他们在浦那地区的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唯一的烹饪燃料来源，室内PM较高私人投资促进局 收集了室内空气PM(来自不吸烟的乡村房屋)。这项提议的主要目标是 描述和比较不同生物质来源(牛粪、木材和作物残渣)的室内PM， 并使用室内PM进行受控的小鼠模型研究，以解剖对肺部和先天的影响 免疫反应，没有臭氧和其他气体成分的混杂影响。结果来自 这项研究将有助于制定未来在农村人口中进行干预以减少肺部疾病的策略。 这项提案是最近颁发的FIRCA合格奖“儿童环境和环境保护”的延伸 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)。项目3 (哮喘的机制--针对环境诱因的饮食干预)，并将检验以下假设 饮食中存在的抗氧化剂，如萝卜硫素，可以通过激活Nrf2来引起化学保护 对抗氧化应激和炎症、保护肺哮喘的途径 小鼠暴露于环境空气颗粒物后的反应。我们当前提案中的具体目标提供了一个 检验我们的假设并研究暴露在空气中的室内PM的生物效应的独特机会 生物质燃料：SA1：收集室内PM并测定不同种类的物理化学特性 在农村家庭中收集的生物质来源。印度农村的家庭使用牛粪、木材、农作物 残留物，或烹饪时三者的组合。我们已经确定了只使用一种生物质的家庭 燃料源。使用这些不同来源的农村家庭室内PM的大小和浓度 正在收集生物质，我们将测定蛋白质、内毒素、金属和有机物质的浓度 这些室内PM样本。这些数据将有助于表征每种燃料来源的相对毒性。 SA2：比较不同来源的生物质衍生的室内PM在农村家庭中收集的效果 肺和先天免疫反应。我们将测试室内PM导致(A)氧化的假设 应激、炎症和呼吸道高反应性，以及(B)抑制先天免疫反应。我们将表演 A/J小鼠不同室内PM样本的肺吸入及氧化应激标志物的测定 支气管肺泡灌洗液和肺组织中的炎性细胞、细胞因子和趋化因子，以及呼吸道高反应性 反应性。我们还将确定巨噬细胞暴露于室内PM是否会抑制巨噬细胞吞噬 细菌。尽管吸入性暴露模型更接近实际，但呼吸道滴注已被证明 是比较样本有限的小鼠相对毒性的一个非常有效的模型。A/J小鼠 之所以选择它们，是因为它们对呼吸道挑战的敏感度更高。

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.