Grant: Project Grant

Exposure to chlorine and its hydrated product hypochlorous acid (bleach) is a cause of asthma and poor control of asthma. It causes an inflammatory response in the airways and an increase in the sensitivity of the airways to stimuli that may cause bronchospasm (narrowing of the bronchial tubes). Certain biochemical substances called leukotrienes are produced within the airways when exposure to chlorine happens. These products have been identified through the study of mice exposed to chlorine. Mice quickly adapt to repeated exposures to chlorine and we have identified novel ways that this adaptation happens We believe that failure to adapt may represent a unique susceptibility that leads to the development of disease. The proposal is aimed at exploring the role of leukotrienes in the "asthma" produced in mice, the mechanism of adaptation and the relevance of the findings to human through controlled low dose exposure of human subjects to chlorine. We anticipate that the studies will allow the identification and testing of new therapies for airway injury caused by oxidative processes.