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认识。这一目标将通过试点研究项目、互动式研究研讨会和博士后前/博士后培养来实现。研究核心4中的具体研究活动属于上面列出的一般研究核心元素的前四个，但在每个广泛的元素中，都有单独的具体目标。这些包括：1)测定可溶性和不溶性颗粒在肺内沉积后的运动；2)暴露的呼吸道组织和细胞的分子遗传学和炎症环境的测定；3)评估这些吸入剂对肺组织和细胞反应影响的病理生理机制；4)从人类接触的健康风险角度解释这些关系；过去，要素2和要素3的主要重点是更好地理解高反应性气道和阻塞性气道疾病的机制，特别强调哮喘。环境污染物如何影响上皮和

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.