title: The Acute Respiratory Distress Syndrome: Mechanisms and Perspective Therapeutic Approaches.
abstract: Acute Respiratory Distress Syndrome (ARDS) is a severe lung inflammatory disorder with a 30-50% mortality. Sepsis and pneumonia are the leading causes of ARDS. On the cellular level there is pulmonary capillary endothelial cell permeability and fluid leakage into the pulmonary parenchyma, followed by neutrophils, cytokines and an acute inflammatory response. When fluid increases in the interstitium then the outward movement continues and protein rich fluid floods the alveolar spaces through the tight junctions of the epithelial cells. Neutrophils play an important role in the development of pulmonary edema associated with acute lung injury or ARDS. Animal studies have shown that endothelial injury appears within minutes to hours after Acute Lung Injury (ALI) initiation with resulting intercellular gaps of the endothelial cells. The Endothelial Cell (EC) gaps allow for permeability of fluid, neutrophils and cytokines into the pulmonary parenchymal space. The neutrophils that infiltrate the lungs and migrate into the airways express pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and contribute to both the endothelial and epithelial integrity disruption of the barriers. Pharmacological treatments have been ineffective. The ARDS Network trial identified low tidal volume mechanical ventilation, positive end expiratory pressure and fluid management guidelines that have improved outcomes for patients with ARDS. Extracorporeal membrane oxygenation is used in specialized centers for severe cases. Prone positioning has recently proven to have significantly decreased ventilator days and days in the intensive care unit. Current investigation includes administration of mesenchymal stem cell therapy, partial fluid ventilation, TIP peptide nebulized administration and the continued examination of pharmacologic drugs.
authors.affiliation: Department of Internal Medicine, Georgia Regents University, USA; Vascular Biology Center, Georgia Regents University, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Gonzales
authors.affiliation: Department of Internal Medicine, Georgia Regents University, USA; Department of Pharmacology and Toxicology, Georgia Regents University, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lucas
authors.affiliation: Department of Internal Medicine, Georgia Regents University, USA; Vascular Biology Center, Georgia Regents University, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Verin
keywords: ARDS biomarkers; ARDS pathology; Acute lung injury; Acute respiratory distress syndrome; Adenosine; Heparin