Pulmonary effects of biomass fuel indoor PM from rural India

描述（由申请人提供）：约有30亿人（占全球人口的一半）暴露于生物质燃料产生的烟雾中，而吸烟的人为10亿人，这表明暴露于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道疾病的最大风险因素。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，并与肺氧化应激和炎症增加有关，并导致城市人口中更严重的呼吸道疾病;然而，由于生物质燃料导致的室内PM对农村人口肺部和先天免疫防御的影响仍不清楚。JHU的PI和合作研究者正在与印度团队的两名主要肺病学家合作，他们在浦那区（马哈拉施特拉邦，印度）的Vadu村建立了一个农村队列，使用生物质燃料作为烹饪燃料的唯一来源，室内PM较高。PI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，木材和农作物残留物）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免疫反应的影响，而不受臭氧和其他气体成分的干扰。这项研究的结果将有助于制定未来的农村人口干预战略，以减少肺部疾病。该提案是最近授予FIRCA合格奖“儿童环境和疾病预防研究中心”P01 ES 018176 -01（项目3，9/1/2009 - 8/31/2014）的延伸。项目3（哮喘饮食干预对环境触发的机制），并将测试这一假设，即饮食中存在的萝卜硫素等抗氧化剂可以通过激活Nrf 2途径来抵消氧化应激和炎症，并防止小鼠在环境空气颗粒暴露后发生肺哮喘反应，从而产生化学保护作用。在我们目前的建议的具体目标提供了一个独特的机会来测试我们的假设，并研究由于暴露于生物质燃料的室内PM的生物效应：SA 1：收集室内PM和确定在农村家庭收集的生物质的不同来源的物理化学表征。印度农村的家庭使用牛粪、木材、作物残渣或三者的组合来做饭。我们已经确定了只使用一种生物质燃料的家庭。正在收集使用这些不同生物质来源的农村家庭室内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。这些数据将有助于描述每种燃料源的相对毒性。SA 2：比较农村家庭收集的各种来源的生物质来源的室内PM对肺部和先天免疫反应的影响。我们将检验室内PM导致（a）氧化应激、炎症和气道高反应性，以及（B）抑制先天免疫反应的假设。我们将在A/J小鼠中进行不同室内PM样品的肺抽吸，并测量氧化应激、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的标志物。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。虽然吸入暴露模型更现实，但气道滴注已被证明是比较样本有限的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的敏感性提高。 公共卫生相关性：约有30亿人（占全球人口的一半）暴露于生物质燃料产生的烟雾中，而吸烟的人则为10亿人，这表明暴露于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道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，并开发一种新的策略来抵消其有害影响。

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.