The National Institute of Environmental Health Sciences and the Office of the Director of the NIH have awarded Hoyle $2.6 million over five years to further his research initially funded in 2006.
Hoyle and his team have identified two medical treatments – rolipram and triptolide – that show promise of treating lung injury from chlorine, a reactive gas highly toxic by inhalation. Rolipram helps with impaired lung function and pulmonary edema – where fluid gets into the lungs, leading to a shortness of breath. It does not affect inflammation. Triptolide, a natural plant product used in traditional Chinese medicine, prevents chlorine-induced lung inflammation but has no effects on other aspects of lung injury.
“We believe an intramuscular injection of rolipram in combination with an anti-inflammatory will represent the most effective countermeasure for chlorine-induced lung injury,” Hoyle said. “It is important that we develop a medical treatment that can be administered quickly to large numbers of patients by first responders or personnel with limited medical training.”
The formulations will be developed by the Southwest Research Institute (SwRI) and evaluated for effectiveness at UofL. Kenneth Carson is leading the formulation effort at SwRI. Andrew Roberts, UofL, and Roy Rando, Tulane University, will work with Hoyle to evaluate the compounds.
“The countermeasures we are developing target aspects of lung injury that are not unique to chlorine exposure, but are also observed after inhalation of other chemical agents such as phosgene, ammonia, sulfur mustard and smoke.
“This research has the potential to develop broad spectrum therapies that could be used against multiple types of chemical threat agents,” Hoyle said.
Chlorine is considered a chemical threat because of the large amounts that are produced and transported in the United States, its ready availability and its toxicity.
The gas is used in a variety of industrial processes, including the production of plastics, solvents, paper products, and purified drinking water. It was first used as a chemical weapon in World War I and most recently during insurgent attacks in the Iraq war. Domestic industrial facilities or rail cars en route are at greatest threat for intentional chlorine release involving an attack.
The Homeland Security Council estimates an attack on an industrial site in an urban area could lead to as many as 17,500 deaths and 100,000 hospitalizations from chlorine exposure.
“These statistics prove the need for effective countermeasures that can be stockpiled, and our work addresses that need,” Hoyle said.