CORE--ENVIRONMENTAL LUNG DISEASE

描述(由申请人提供)：本研究核心的总体目标是发展和促进对城市空气污染对人体影响的新理解。这一目标将通过试点研究项目、互动研究研讨会和博士后/博士后培训来实现。研究核心4中的具体研究活动属于上述一般研究核心要素中的前四项，但在每个主要要素中，都有各自的具体目标。这些内容包括：1)测定可溶和不溶颗粒在肺中沉积后的运动；2)测定暴露在空气中的呼吸道组织和细胞的分子遗传和炎症环境；3)评估与这些吸入剂对肺组织和细胞反应的影响有关的病理生理机制；4)从人体暴露的健康风险角度解释这些关系；过去要素2和3中的一个主要重点是更好地了解高反应性呼吸道和阻塞性呼吸道疾病的机制，特别强调哮喘。环境污染物如何影响上皮细胞和 呼吸道平滑肌与哮喘患者呼吸污染空气的反应有直接关系。在市中心，这样的空气污染会导致一种被称为城市哮喘的疾病。这项研究和第一个核心要素中的研究将构成新的、越来越多的外延重点的科学基础，涉及研究核心1中的人类暴露评估研究。由埃格尔斯顿博士领导的约翰·霍普金斯城市环境中儿童哮喘中心也可能为与这种人类病理相关的新的机械论理解提供机会。市中心患肺气肿和肺癌的风险也很高，与研究核心3合作的核心新项目将开始研究这些病理的潜在机制。最后，将扩大的一个日益重要的方向是空气污染与病毒感染的相互作用。拥有免疫学专业知识的两名新核心教员(Jacoby和Imani)将领导这项工作。长距离飞行 研究的核心目标是能够调查与各种城市空气污染物有关的这一系列问题，从暴露程度的定量分析到对细胞和组织对这些暴露的基本病理生理反应的定量了解。目前，研究核心内的这一全球方法在臭氧、颗粒物和病毒感染方面发展得相当好，研究范围从分子遗传学到人类接触。需要强调的是，这个核心的成员是生理学家、药理学家、免疫学家、病理学家和肺部内科医生，他们研究环境对肺的侮辱的基本机制。如上所述，研究人员认为这种多学科背景是该研究核心的一大优势，为NIEHS中心提供了关于环境研究的独特视角。

Description (provided by applicant): The overall objectives of this Research Core are to develop and promote new understandings of the effects of urban air pollution on the human body. This goal will be implemented by pilot research projects, interactive research seminars, and pre/postdoctoral student training. Specific research activities in Research Core 4 fall within the first four of the general Research Core elements listed above, but within each broad element, there are individual specific aims. These include: 1) Determination of the movement of soluble and insoluble particles after deposition in the lung; 2) Determination of the molecular genetic and inflammatory environment of exposed respiratory tissues and cells; 3) Evaluation of the pathophysiologic mechanisms associated with the effects of these inhalants on pulmonary tissues and cellular responses; and 4) Interpretation of these relations in terms of health risks from human exposures; a major focus within elements 2 and 3 in the past has been a better understanding of the mechanism of hyperreactive airways and obstructive airway diseases, with special emphasis on asthma. How environmental pollutants affect the epithelium and airway smooth muscles has direct relevance to the response of asthmatics breathing in polluted air. In the inner cities such air pollution can lead to a condition known as urban asthma. This research, along with that in the first Core element, will form the scientific basis for new and increasing outreach focus involving the human exposure assessment research in Research Core 1. The Johns Hopkins Center for Childhood Asthma in the Urban Environment, headed by Dr. Eggleston, also may provide opportunity for new mechanistic understandings related to this human pathology. Risks for emphysema and lung cancer are also high in inner cities, and new projects in the Core with collaboration with Research Core 3 will begin to look at underlying mechanisms of these pathologies. Finally an increasingly important direction that will be expanded is the interaction of air pollution with viral infections. Two new faculty members (Jacoby and Imani) to the Core with immunologic expertise will lead this effort. A long range Research Core aim is to be able to investigate this spectrum of questions related to a variety of urban airborne pollutants, from the quantitative analysis of the exposure magnitude to a quantitative understanding of basic pathophysiologic responses of cells and tissues to these exposures. At the present time this global approach within the Research Core is fairly well developed for ozone, particulate matter, and viral infections, with studies spanning the spectrum from molecular genetics to human exposures. It is important to emphasize that the members of this Core are physiologists, pharmacologists, immunologists, pathologists, and pulmonary physicians who investigate basic mechanisms underlying environmental insults to the lung. As noted above, the investigators feel that this multi-disciplinary background is a major strength of this Research Core, providing the NIEHS Center with a unique perspective on environmental studies.