Abstract
Acute lung injury (ALI) and severe sepsis are common critical illnesses associated with the mobilization of bone marrow-derived cells into the circulation. By identifying and determining these cells' functional characteristics, unique prognostic biomarkers can be developed to help investigators understand the mechanisms underlying the pathophysiology of these disorders. We previously demonstrated an increased colony-forming unit (CFU) ability of circulating peripheral blood mononuclear cells (PBMCs) in patients with ALI, compared with healthy control subjects, that also correlated with improved survival. Here we hypothesized that the increased CFUs in ALI are associated with lung injury, and therefore ALI will result in an increased number of CFUs compared with patients exhibiting severe sepsis. To test this, blood was collected from 80 patients (63 with ALI, and 17 with severe sepsis) within 72 hours of diagnosis, and from 5 healthy control subjects. A CFU assay was performed on isolated PBMCs. Lung injury scores and the need for mechanical ventilation were greater in patients with ALI than in patients with severe sepsis (P < 0.0001 for each). CFU numbers were highest in patients with ALI compared with patients manifesting severe sepsis or control subjects (median CFU number [25-75% quartiles] of 61 [13-104] versus 17 [3-34] versus 5 [2-13], P < 0.0005). A trend toward improved survival was demonstrated in patients with high (> or = 48) CFUs (P = 0.06). No relationship between CFUs and mechanical ventilation was evident. Our findings suggest that increased colony-forming ability by PBMCs in ALI results from lung injury, independent of sepsis and mechanical ventilation. Factors contributing to colony formation by PBMCs in ALI, and the role PBMCs play in its pathogenesis remain to be fully established.