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）：大约30亿人口，全球人口一半，与生物量燃料中的烟雾相比，与10亿人吸烟的人相比，这表明暴露于生物质烟雾可能是呼吸疾病的最大危险因素，例如慢性阻塞性肺部疾病（COPD），哮喘和呼吸道感染。在印度农村使用生物质进行烹饪的非吸烟者中，COPD和哮喘的增加不成比例。对环境空气颗粒物（PM）进行了充分的研究，并与增加的肺氧化应激和炎症有关，并在城市人口引起更大的呼吸道疾病。但是，由于生物量燃料对肺部和农村人口的先天免疫防御的影响尚不清楚。 JHU的PI和共同投资者正在与印度团队的两位主要肺科医生合作，他们在浦那村（Maharashtra，印度马哈拉施特拉邦）建立了一个农村队列，使用生物量燃料作为其唯一的烹饪燃料来源，并使用高室内PM进行烹饪燃料。 PI收集了室内空气PM（来自没有吸烟者的农村房屋）。该提案的主要目的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，以剖析对肺部和先天免疫反应的影响，而没有臭氧和其他气体成分的混淆作用。这项研究的结果将有助于制定未来在农村人群减少肺部疾病的策略。该提案是最近授予的FIRCA奖项“儿童环境和疾病预防研究中心”的延伸。项目3（针对环境触发因素的哮喘角度干预措施的机制）将检验以下假设：饮食中存在的抗氧化剂（如磺胺硫烷）可以通过激活NRF2途径来抵消氧化应激和炎症，并防止肺部空气颗粒曝光后，通过激活NRF2途径来引起化学保护。当前建议中的具体目的为检验我们的假设提供了独特的机会，并研究了由于暴露于生物量燃料而导致的室内PM的生物学作用：SA1：收集室内PM并确定在农村房屋中收集的不同生物量的物理化学表征。印度农村的房屋使用牛粪，木材，农作物残留物或三个组合进行烹饪。我们已经确定了仅使用一个生物质燃料来源的房屋。正在收集使用这些不同生物量来源的农村房屋中室内PM的大小和浓度，我们将确定这些室内PM样品中的蛋白质，内毒素，金属和有机浓度。这些数据将有助于表征每个燃料源的相对毒性。 SA2：比较在肺部和先天免疫反应中收集在农村房屋中的生物质界室内PM的各种源的影响。我们将检验以下假设：室内PM引起（a）氧化应激，炎症和气道高反应性，并且（b）抑制先天免疫反应。我们将在A/J小鼠中对不同室内PM样品进行肺抽吸，并测量氧化应激的标记，支气管肺泡灌洗和肺中的炎性细胞，细胞因子和趋化因子以及气道超反应性。我们还将确定巨噬细胞暴露于室内PM是否抑制细菌的吞噬作用。尽管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，用于比较样品受到限制的小鼠的相对毒性。之所以选择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：大约30亿人口，全球人口一半，暴露于生物质燃料中的烟雾，而烟烟的十亿人则表明，暴露于生物质烟雾可能是呼吸道疾病的最大危险因素，例如慢性阻塞性肺部疾病（COPD），哮喘和呼吸道感染。这些研究将确定使用生物量进行烹饪的房屋空气中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作用。