Pulmonary effects of biomass fuel indoor PM from rural India

项目摘要 约有30亿人，即世界人口的一半，暴露在生物质燃料产生的烟雾中， 10亿人吸烟，这表明接触生物质烟雾可能是最大的风险 慢性阻塞性肺疾病（COPD）、哮喘和呼吸道疾病等呼吸系统疾病的影响因素 全球感染。农村地区非吸烟者中COPD和哮喘的发病率不成比例地增加 印度使用生物质做饭。环境空气颗粒物（PM）已得到充分研究，并与增加的 肺氧化应激和炎症，在城市人口中引起更严重的呼吸道疾病; 然而，在农村，由于生物质燃料引起的室内PM对肺和先天免疫防御的影响 人口仍不清楚。来自JHU的PI和合作研究者正在与两个关键的 来自印度团队的肺科医生在浦那区的Vadu村建立了一个农村队列， （马哈拉施特拉邦，印度）使用生物质燃料作为其具有高室内PM的烹饪燃料的唯一来源。法律与正义党 收集了室内空气PM（来自非吸烟者的农村房屋）。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、木材和作物残留物）的室内PM， 并使用室内PM进行对照小鼠模型研究，以剖析对肺部和先天性 没有臭氧和其他气体成分的干扰作用的免疫反应。的结局 这项研究将有助于制定未来的农村人口干预战略，以减少肺部疾病。 这项建议是最近颁发的FIRCA合格奖“儿童环境和 疾病预防研究中心”P01 ES 018176 -01（项目3，2009年9月1日至2014年8月31日）。项目3 （哮喘饮食干预对环境触发的机制），并将测试假设， 饮食中存在的萝卜硫素等抗氧化剂可以通过激活Nrf 2来引起化学保护作用。 对抗氧化应激和炎症并防止肺哮喘的途径 小鼠暴露于环境空气颗粒物后的反应。我们现时建议的具体目的， 这是一个独特的机会来测试我们的假设，并研究室内PM的生物效应，由于暴露于 生物质燃料：SA 1：收集室内PM并确定不同生物质燃料的理化特性。 农村家庭收集的生物质来源。印度农村的家庭使用牛粪、木材、农作物 残渣，或三者的组合用于烹饪。我们已经确定了只使用一种生物质的家庭 燃料来源。在使用这些不同来源的农村家庭中，室内PM的大小和浓度 生物量正在收集，我们将确定蛋白质，内毒素，金属和有机物的浓度， 这些室内PM样本这些数据将有助于描述每种燃料源的相对毒性。 SA 2：比较在农村家庭收集的各种生物量来源的室内PM的影响 对肺部和先天免疫反应的影响我们将测试室内PM导致（a）氧化 应激、炎症和气道高反应性，和（B）抑制先天免疫应答。我们将执行 A/J小鼠肺吸入不同室内PM样品并测量氧化应激标志物， 支气管肺泡灌洗液和肺中的炎性细胞、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是否会抑制巨噬细胞对 细菌虽然吸入暴露模型更现实，但气道滴注已被证明 是一个非常有效的模型，比较相对毒性的小鼠样品有限。A/J小鼠 因为他们对气道挑战的高度敏感性而被选中。

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.