EARLY DETECTION OF TYPE-III PROCOLLAGEN PEPTIDE IN ACUTE LUNG INJURY - PATHOGENETIC AND PROGNOSTIC-SIGNIFICANCE

The fibroproliferative reaction to acute lung injury may limit restora tion of normal lung function and increase mortality in patients with a cute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and f or identifying patients with acute lung injury who are at high risk fo r death and might benefit from new therapeutic modalities. Using an im munoassay, type III procollagen NH2 terminal peptide was measured in t he pulmonary edema fluid of 44 patients with either acute lung injury or hydrostatic pulmonary edema (control group) within the first 24 h a fter endotracheal intubation for acute respiratory failure. Patients w ith acute lung injury (n = 33) or hydrostatic edema (n = 11) had the s ame degree of lung dysfunction as measured by the severity of oxygenat ion defect, the level of positive end-expiratory pressure, the decreas e in static lung compliance, and the extent of infiltrates on the ches t radiograph. However, the median procollagen III level was 5-fold hig her in the pulmonary edema fluid of patients with acute lung injury th an in the patients with hydrostatic pulmonary edema (p = 0.0001). Of t he 33 patients with acute lung injury, 21 patients died and 12 lived. Nonsurvivors had significantly higher procollagen III levels than did survivors (p = 0.05). The positive and negative predictive values for nonsurvival for a procollagen III level greater than or equal to 1.75 U/ml were 74 and 83%, respectively. The relative risk of dying in the presence of a procollagen III value greater than or equal to 1.75 U/ml was 4.5 (95% CI, 0.7 to 27). Collagen synthesis in the lung, as refle cted by elevated levels of procollagen III in pulmonary edema fluid, b egins within the first 24 h of acute lung injury concurrent with the a cute phase of increased endothelial and epithelial permeability to pro tein. This evidence suggests that fibrosing alveolitis begins much ear lier in the course of clinical acute lung injury than has previously b een appreciated. In addition, the presence of an elevated level of pro collagen III is an early predictor of poor outcome. Thus, elevation of procollagen III in pulmonary edema fluid may have both pathogenetic a nd prognostic significance in patients with acute lung injury.