The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome


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Abstract

ObjectivesTo determine the concentrations of proinflammatory mediators, collagenases, and procollagen type III peptides in undiluted pulmonary edema fluids and in plasma obtained in patients with early acute respiratory distress syndrome (ARDS) and in control patients with hydrostatic lung edema; and to assess the relationship between these inflammatory and profibrotic markers.DesignA prospective, clinical study with measurements of inflammatory markers in pulmonary edema fluids and in paired plasma samples.SettingA medical intensive care unit.PatientsPatients intubated with lung permeability (n = 23) and hydrostatic (n = 8) pulmonary edema were prospectively enrolled in the study. The severity of the disease at the time of intubation was assessed, using the Simplified Acute Physiological Score (SAPS) II and the Lung Injury Score (LIS).InterventionsPlasma and undiluted edema fluids were obtained at the time of intubation with pulmonary edema requiring mechanical ventilation; and in some patients, a second edema fluid sample was collected a few hours later.Measurements and Main ResultsProinflammatory activity, dependent on the presence of bioactive proinflammatory cytokines, interleukin (IL)-8, and neutrophil matrix metalloproteinase (MMP)-9 were significantly increased in ARDS fluids compared with plasma or control fluids from patients with congestive heart failure. In contrast, MMP-2, originating from lung cells other than phagocytes, was slightly increased in ARDS edema fluids compared with plasma, but similar to levels found in hydrostatic edema fluids. Proinflammatory activity was undetectable in plasma from ARDS patients. Levels of procollagen peptide III, a marker of collagen synthesis, were increased in permeability edema fluids compared with hydrostatic edema fluids or plasma, confirming that alveolar collagen synthesis begins very early and in parallel with acute inflammation in ARDS. Control patients with hydrostatic edema had similar SAPS II and LIS scores compared with ARDS patients.ConclusionsThese results strongly support the conclusion that during the early phase of ARDS, the lung is the site of an intense inflammatory process with sequential activation of cytokines, chemokines, and secretion of proteases, as well as concomitant collagen synthesis. The inflammation is mostly limited to the lung, with low levels of inflammatory mediators in the systemic circulation. Unlike clinical scoring systems (SAPS II and LIS), inflammatory markers differentiate patients with permeability and hydrostatic pulmonary edema. (Crit Care Med 1999; 27: 304-312)

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