Abstract
Background Excessive inflammation leading to increased alveolar-capillary barrier permeability remains the pathogenic model for acute respiratory distress syndrome (ARDS). Alveolar macrophage (AM) polarization has been shown to modify the activity of various matrix metalloproteinases (MMPs) that have downstream effects on key ARDS cytokines/chemokines, however the relationship between AMs, MMP28 (the newest member of the MMP family), and ARDS clinical outcomes is unknown.Methods We analyzed bronchoalveolar lavage fluid (BALF) and peripheral blood from subjects previously enrolled in a phase-II trial of omega-3 fatty acids for the treatment of ARDS ( n = 76). In a subset of these patients ( n = 25), we tested for assocations between AM- and peripheral blood monocyte (PBM)-specific MMP28 gene expression and clincal outcomes [ventilator-free days (VFDs), P a O 2 /F i O 2 ratio (P/F ratio), and sequential organ failure assessment score (SOFA)]. We tested for assocations between soluble BALF or plasma MMP28 concentrations and ARDS clinical outcomes and inflammatory mediator concentrations in the entire cohort.Results Increased AM MMP28 gene expression was significantly associated with worse VFDs and P/F ratio ( p < 0.05). Higher BALF MMP28 concentrations were associated with worse P/F, but not VFDs. Increased BALF MMP28 concentrations were associated with increased % neutrophils as well as BALF total protein, IL-6, IL-17A, and MCP-1 concentrations (all p < 0.05). Plasma MMP28 concentrations were not associated with any clinical outcome. Increased PBM MMP28 gene expression was associated with worse P/F ratio but not VFDs.Conclusions Higher AM MMP28 gene expression and BALF MMP28 concentrations are associated with poor clinical outcomes and with increased alveolar inflammatory mediators in patients with ARDS.
Heat shock protein 70 and the acute respiratory distress syndrome
