Konstantin Birukov, MD, PhD

Can a Drug Used to Protect Against Radiation Damage Also Treat Lung Injury?

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are types of severe, acute lung dysfunction affecting all or most of both lungs that occurs as a result of illness or injury. ARDS has a death rate of 30-40%. Despite recent progress in treatment of acute lung injury, there is still no successful strategy to reduce lung damage and tissue injury in this condition.

Dr. Birukov studied the compound amifostine, a drug used to control some side effects of chemotherapy and radiation therapy, to see whether it could significantly reduce acute lung injury induced by infectious agents. Amifostine belongs to a group of drugs called cytoprotectants, which protect normal tissue from some of the side effects caused by some treatments for cancer.

His research, supported by an American Lung Association Career Investigator Award, demonstrated a protective effect of amifostine on acute lung injury induced by infectious agents. In addition to immediate beneficial effects on disease processes triggered by bacteria in the lung, he also discovered that preventive treatment with much lower doses of amifostine stimulates the body’s own antioxidant defense mechanisms and increases resistance to ventilator induced lung injury (VILI). He discovered the mechanisms underlying amifostine’s protective effects, which may be used to develop novel clinical therapies for the treatment of ALI and VILI.

“American Lung Association awards granted to me and two other recipients, Patrick Singleton and Anna Birukova, allowed us to enhance and extend our research programs, and our interactions were a key element in organizing the Lung Injury Center with the valuable support of the Pulmonary Section and The University of Chicago Department of Medicine,” he says. “Our Center’s major mission is lung research and training the next generation of young scientists.”

Publications:

Fu P, Birukova AA, Sammani S, Burdette DO, Murley JS, Garcia JGN, Grdina DJ, Birukov KG. The protective role of amifostine in preventing LPS-induced acute lung injury. Resp. Crit. Care Med. 175:A783, 2007.

Birukova AA, Cokic I, Moldobaeva N, Birukov KG. Amifostine reduces lypopolysacharide-induced lung dysfunction via suppression of redoxsensitive inflammatory signaling. Proceedings of the European Respiratory Society; October 2008

Fu P, Birukova AA, Xing J, Sammani S, Murley JS, Garcia JG, Grdina DJ, Birukov KG. Amifostine reduces lung vascular permeability via suppression of inflammatory signaling. Eur Respir J. 2009; 33(3):612-24.

Birukov KG. Cyclic stretch, reactive oxygen species and vascular remodeling. Antioxidants & Redox Signaling, 2009; 11(7): 1651-1667.

Fu P, Murley JS, Grdina DJ, Birukova AA, Birukov KG. Induction of cellular antioxidant defense by amifostine improves ventilator-induced lung injury. Crit Care Med, 2011 Dec;39(12):2711-21.

Birukov KG. “Ventilator induced mechanical stress and lung vascular dysfunction”. In: Textbook on Vascular Disease; J. X. – J. Yan et al. (eds.). Springer Science., DOI 10.1007/978-0-387-87429-6_64, 2011