More than $2 million in funding from the National Heart, Lung, and Blood Institute will assist John Christman, MD, and fellow
researchers at The Ohio State University’s Dorothy M. Davis Heart and Lung Research Institute in funding research into novel treatments for acute respiratory distress syndrome (ARDS) that target lung macrophages.
ARDS is a condition in which lungs lose barrier functions, allowing protein-rich fluids to leak into the lungs, which results in low blood oxygen level and failure of the body’s vital organs and requires life support. The most common cause of ARDS is severe sepsis, but it can also be caused by polytrauma, pneumonia, massive hemorrhage and inflammation of the pancreas. There are are currently treatments that accelerate the recovery of patients with ARDS, such as conservative fluid management and a gentle form of mechanical ventilation, which lessen the severity of the condition.
Christman, along with fellow investigators Manjula Karpurapu, PhD, and Dehua Pei, PhD, are investigating the role of lung macrophages (cells in the immune system), that may prevent the development of ARDS in accelerate the recovery of established ARDS. The proposal is based on the scientific premise that inflammatory macrophages can accentuate ARDS, whereas counter-inflammatory macrophages can accelerate the recovery from ARDS. These investigators have focused on nuclear fat of activated T cells (NFAT) transcription in cells, which play a key role in regulating the inflammatory phenotype of lung macrophages. When NFAT is activated in sepsis, macrophages disrupt the permeability barrier of the lungs initiating ARDS and respiratory failure. The researchers are developing an interdiction to block and stop ARDS by regulating the macrophage inflammatory phenotype.
The drug development studies are currently in the preclinical stage, and researchers hope to move to clinical trials and eventually to market. The grant extends through 2021, and has been reviewed locally with widespread praise. Other members of the team include Sangwoon Chung, PhD, Yong Gyu Lee, and Patrick Dougherty.