ABSTRACT
Sepsis, a systemic condition with several stages and degrees of severity resulting from dysregulated activation of the innate immune and hemostatic systems, is a lethal syndrome and a major cause of acute lung injury (ALI) and its progression to the acute respiratory distress syndrome (ARDS). The concept that sepsis can lead to end organ injury and dysfunction dates to the Greek origin of the term (sepsios) and to investigations of its pathogenesis that predate modern times (1). Although not reported as a cause of lung injury in the 12 patients in the seminal description of ARDS (2), sepsis was later recognized as a major inciting factor by Petty and coworkers (3). In addition, many subsequent reports demonstrated an association between sepsis and ALI, and recent reviews identify it as the leading condition that “triggers” the molecular and cellular cascades that culminate in ALI and ARDS in humans (4-12). Sepsis-induced ALI and ARDS can be caused by infection with gram-positive bacteria, gram-negative organisms, or fungi, although in many series gram-negative bacterial infection dominates (4). Circulating bacterial lipopolysaccharide (LPS) has been associated with development of ARDS induced by diverse predisposing conditions in some, but not all, studies, indicating that it may act in an additive or synergistic fashion with trauma, hemorrhage, and other insults to induce alveolar-capillary membrane injury (13, 14). However, here we will focus for the most part on syndromes in which sepsis is presumed to be the principal or only inciting condition for ALI and ARDS.
