A five-year program is planned for developing the candidate as an independent investigator and establishing a clinical research program. The first three years will continue the condidate's training in the area of mechanisms of acute lung reactions to environmental agents. Characterization and localization of the acute airways response to ozone will be the focus for a series of clinical and animal studies. Harold A. Menkes, M.D. will serve as primary preceptor. Gareth Green, M.D., N. Robert Frank, M.D., and Edward A. Emmett, M.D. will be secondary preceptors. An initial study of the response to inhaled ozone will be completed at the Environmental Protection Agency CLEANS facility in Chapel Hill, N.C. The hypotheses to be tested are 1) that the large airways response to inhaled ozone is a neural reflex mechanism blocked by inhaled atropine, and 2) that an acute peripheral (small airways) response to ozone at 0.4 ppm can be detected by pulmonary function testing. Other human studies will then be undertaken with Dr. Frank at the environmental exposure chamber at the University of Maryland (Baltimore) evaluating differential susceptibility to ozone between asthmatics and non-asthmatics and risk for susceptibility to inhaled ozone on the basis of sex and smoking status. Parallel studies will be conducted in the animal physiology and toxicology laboratories with the dog model of acute airways response to inhaled ozone investigating 1) penetration and absorption gradients of ozone in the large and small airways and 2) the relationship (time of onset, degree, mechanism, duration, adaptation, tolerance, and sequelae) of the acute large airways response to the small airways response. The final two-year period will be used to establish a clinical research program in environmental and occupational lung disease at the Johns Hopkins Medical Institutions continuing to utilize the Center for Occupational and Environmental Health and the University of Maryland exposure chamber.
