The pulmonary physician in critical care c 6: The pathogenesis of ALI/ARDS

Lung injury is the term used to describe the pulmonary response to a broad range of injuries occurring either directly to the lung or as the consequence of injury or inflammation at other sites in the body. Acute respiratory distress syndrome (ARDS) represents the more severe end of the spectrum of this condition in which there are widespread inflammatory changes throughout the lung, usually accompanied by aggressive fibrosis. The pathogenesis of lung injury is not well understood. 5 We do not know why some people progress to ARDS while others who sustain indistinguishable injuries remain relatively unaffected. ARDS is unique among pulmonary fibrotic conditions in that the fibrosis resolves almost completely in many cases; once again the mechanisms for this are not understood. It is now well recognised that some of the damage is created and exacerbated by mechanical ventilation. However, mortality from ARDS has improved in certain centres over the last 10 years, 10 predating major changes in ventilatory practice; the reasons for this improvement in mortality are thus also not clear. ARDS often occurs as part of a wider picture of multiorgan dysfunction syndrome (MODS). Central to the pathogenesis are an explosive inflammatory process and the reparative responses invoked in an attempt to heal this. This review will outline the pathological processes which occur during ARDS and their evolution as our understanding of the inflammatory, immune, and fibroproliferative responses has grown. It will describe the underlying cellular and molecular processes, correlate these with the clinical picture, and highlight how such insights can lead to novel therapeutic approaches.