Advances in understanding of the pathogenesis of acute respiratory distress syndrome.
The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. The resulting loss of gas exchange leads to acute respiratory failure and typically catastrophic illness, termed acute respiratory distress syndrome (ARDS), requiring ventilatory and critical care support. There remains a significant disease burden, with some estimates showing 200,000 cases each year in the USA with a mortality approaching 50%. In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.
Academic Respiratory Unit, University of Bristol, Southmead Hospital, Westbury-on-Trym, UK.
Charles
C
Sharp
Ann B
AB
Millar
Andrew R L
AR
Medford
D000328:Adult; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases