Supplement: Center for Appalachian Research in Environmental Sciences: Community Engagement Core

The research proposed in this Administrative Supplement application aims to uncover the role of neurogenic mechanism in the acute lung injury caused by accidental exposure to chlorine gas (Cl2). Because of its widespread use as a chemical agent in various industrial operations, Cl2 is one of the most common and toxic inhaled irritants. More importantly, numerous incidences resulting from accidental release of large quantities and high concentrations of Cl2 from industrial facility into the environment have led to severe lung injuries and fatalities. Inhalation of Cl2 at high concentration even for a short duration evoked cough, bronchospasm, difficulty in breathing and asthma-like symptoms in healthy individuals. Although activation of airway sensory nerves is believed to be involved in the manifestation of these symptoms, it is not yet known whether inhaled Cl2 gas exerts a stimulatory effect on vagal bronchopulmonary C-fiber afferents, the dominant type of sensory nerves innervating the respiratory tract and playing a pivotal role in defending the lung against inhaled chemical irritants. This proposed study focuses on two specific aims: 1) to determine if inhalation of a high concentration of Cl2 gas generated a stimulatory effect on vagal bronchopulmonary C-fiber sensory nerves; and to establish the concentration-response curve and the threshold concentration of Cl2 in evoking this stimulatory effect; 2) to investigate if exposures to high concentrations of Cl2 triggers the release of tachykinins from bronchopulmonary C-fiber endings and cause neurogenic inflammation and edema in the lung and airways. The proposed studies will be carried out in Sprague-Dawley rats and completed in one year with the support of Analytical Core and Integrated Health Sciences Facilities Core of the parent grant (P30-ES026529). If our hypotheses are proven correct, it will uncover a significant role of tachykinins released from vagal bronchopulmonary C-fiber sensory nerves in the pathogenesis of lung/airway injury following accidental exposure to high concentration of Cl2. Results obtained from this study may lead to the discovery of promising new therapeutics for reducing the mortality and morbidity caused by this toxic environmental agent.