Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is an acute, severe injury to the lungs which affects approximately 150,000 people in the United States each year.* Numerous clinical conditions such as pneumonia, sepsis, severe trauma and inhalation of gastric contents, and less commonly other direct and indirect lung injuries, are all associated with the development of acute respiratory disease syndrome.

Despite numerous advances in the supportive care of patients via alternative approaches in mechanical ventilation, the mortality associated with ARDS remains at 32 to 45% as compared with 53 to 68% in the 1980s.^ On average, surviving patients still spend at least two weeks in intensive care units during the treatment and recovery phase and while in the majority of patients, pulmonary function returns to normal, this may take anywhere from 6 to 12 months.

An initiating event in the development of ARDS is the increase in permeability of the lung microcirculation and subsequent exudation of plasma proteins and inflammation. We have studied the ability of cell-based gene therapy with angiopoietin-1 (Ang1) to reduce lung vascular inflammation and permeability using the lipopolysaccharide-induced injury model in Fisher 344 rats. These initial experiments used rat skin fibroblasts, however we are now testing the ability of EPCs, with and without genetic manipulation utilizing transfection with Ang-1 and potentially with hemeoxygenase (HOX), to repair the vascular damage and reduce inflammation in this model.

* Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49.

^ Udobi KF, Childs E, Touijer K. Acute respiratory distress syndrome. Am Fam Physician. 2003 Jan 15;67(2):315-22.