The overall goal of this research core is to determine predictors of human responsiveness to specific pollutants in the urban environment. This knowledge will be used to set standards, but also can be used for the treatment of airway disease that may be induced by these agents. The fundamental aims of this core are to: 1) investigate the delivery of inhaled particles and pollutants to the respiratory system; 2) determine the molecular genetic and inflammatory susceptibility of exposed respiratory tissues and cells; 3) evaluate the pathophysiologic mechanisms associated with the effects of these inhalants on pulmonary tissues and cellular responses; 4) assess the health risks of these agents to human populations; and 5) train students and fellows in pathophysiologic research related to problems in environmental health. The core consists of individuals with expertise in the mechanisms of uptake into respiratory tissue, experimental assessment of pulmonary function in humans, experimental assessment of acute and chronic forms of inflammation, genetic factors that determine susceptibility, and evaluation of asthma in the urban population. The accomplishments of this core during the previous 5 year funding period are profound. Dr. Swift has used radon aerosols to further understand deposition in the upper airway. Dr. Laube has investigated the effect of asthma on deposition and clearance of aerosols. Dr. Jakab has shown that inert particles change the deposition of gases in the lung. Dr. Kleeberger has shown that genetic predisposition to ozone exists in inbred mice, with susceptibility largely controlled by a single recessive gene. Dr. Wills-Karp is also studying the genetic regulation of airway reactivity in inflamed airways, especially as it relates to Th2 cytokines. Under the direction of Dr. Mitzner, important and substantial contributions have been made regarding airway physiology, smooth muscle, contractility, and airway imaging. Collaborative studies between Drs. Foster and Brown have led to a more fundamental understanding of the heterogeneous airway response to inhaled ozone. Innovative studies by Dr. Croxton have shown that ozone directly affects ion channel activity of the airway epithelia. Human studies include the deposition of fine particles in asthmatic and normal subjects, injury and repair mechanisms in the airway epithelia, and the use of exhaled air as a biomarker for pollutant oxidant exposure. The Core investigators and facilities have resulted in substantial recruitment of students and fellows to environmental projects within the NIEHS Center. In the future, greater efforts will be made to expand the translation of fundamental scientific knowledge to the community. Plans are made to interact more regularly with Dr. Eggleston, a practitioner who specializes in asthma. In addition, expansion into the area of molecular biology will be promoted through the use of other research cores and facilities from the NIEHS Center. New areas of investigation will include: 1) imaging studies to investigate local transport of aerosol particles in the airway lumen; and 2) genetic studies designed to localize the genes that play a role in the response to environmental toxins.
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