ABSTRACT
I. Introduction In a landmark 1967 article published in Lancet, Ashbaugh and coworkers formally introduced the medical community to the syndrome of “acute respiratory distress in adults,” or ARDS (1). This article described a pattern of clinical findings common to patients with respiratory failure due to a wide range of inciting injuries. ARDS was characterized histologically as protein-rich pulmonary edema with neutrophilic infiltration and hemorrhage (2,3). Over the ensuing two decades, distinct pathological phases in the development of ARDS were described, including an initial exudative phase characterized by cell injury and vascular leak (4), and a later “fibroproliferative” phase. The fibroproliferative phase was defined by chronic inflammation, fibrosis, and neovascularization (2,5). The dividing line between the acute exudative phase and the late fibroproliferative phase is not easily demarcated, and in the absence of lung biopsy tissue, this division must largely be inferred from chronicity. For the purposes of clinical trials, the term “persistent ARDS” has been used to describe patients meeting the criteria for ARDS and requiring mechanical ventilation seven or more days (6). It is presumed that persistent impairment of gas exchange and poor lung compliance more than one week after onset of ARDS correlates with progressive fibrosis (4). Variability among individuals exists, however, with some patients demonstrating relatively little fibrosis and others evincing ongoing neutrophilic inflammation well beyond the first week after symptom onset (7,8). It is therefore perhaps more accurate to consider exudation, inflammation, cell necrosis, and fibroproliferation as overlapping facets of the response to acute lung injury rather than as temporally distinct phases.
