Chesnutt A N, Matthay M A, Tibayan F A, Clark J G
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):840-5. doi: 10.1164/ajrccm.156.3.9701124.
The fibroproliferative reaction to acute lung injury may limit restoration of normal lung function and increase mortality in patients with acute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and for identifying patients with acute lung injury who are at high risk for death and might benefit from new therapeutic modalities. Using an immunoassay, type III procollagen NH2 terminal peptide was measured in the pulmonary edema fluid of 44 patients with either acute lung injury or hydrostatic pulmonary edema (control group) within the first 24 h after endotracheal intubation for acute respiratory failure. Patients with acute lung injury (n = 33) or hydrostatic edema (n = 11) had the same degree of lung dysfunction as measured by the severity of oxygenation defect, the level of positive end-expiratory pressure, the decrease in static lung compliance, and the extent of infiltrates on the chest radiograph. However, the median procollagen III level was 5-fold higher in the pulmonary edema fluid of patients with acute lung injury than in the patients with hydrostatic pulmonary edema (p = 0.0001). Of the 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 > or = 1.75 U/ml were 74 and 83%, respectively. The relative risk of dying in the presence of a procollagen III value > or = 1.75 U/ml was 4.5 (95% CI, 0.7 to 27). Collagen synthesis in the lung, as reflected by elevated levels of procollagen III in pulmonary edema fluid, begins within the first 24 h of acute lung injury concurrent with the acute phase of increased endothelial and epithelial permeability to protein. This evidence suggests that fibrosing alveolitis begins much earlier in the course of clinical acute lung injury than has previously been appreciated. In addition, the presence of an elevated level of procollagen III is an early predictor of poor outcome. Thus, elevation of procollagen III in pulmonary edema fluid may have both pathogenetic and prognostic significance in patients with acute lung injury.
急性肺损伤后的纤维增生反应可能会限制肺功能恢复正常，并增加急性肺损伤患者的死亡率。肺中胶原蛋白合成的生物标志物可能有助于研究急性肺损伤的发病机制，并识别出急性肺损伤中具有高死亡风险且可能从新治疗方法中获益的患者。采用免疫测定法，对44例因急性呼吸衰竭行气管插管后24小时内患有急性肺损伤或静水压性肺水肿（对照组）患者的肺水肿液中的III型前胶原NH2末端肽进行了检测。急性肺损伤患者（n = 33）或静水压性肺水肿患者（n = 11）的肺功能障碍程度相同，这通过氧合缺陷的严重程度、呼气末正压水平、静态肺顺应性降低以及胸部X线片上浸润范围来衡量。然而，急性肺损伤患者肺水肿液中的前胶原III中位数水平比静水压性肺水肿患者高5倍（p = 0.0001）。在33例急性肺损伤患者中，21例死亡，12例存活。非存活者的前胶原III水平显著高于存活者（p = 0.05）。前胶原III水平≥1.75 U/ml时，非存活的阳性和阴性预测值分别为74%和83%。前胶原III值≥1.75 U/ml时死亡的相对风险为4.5（95% CI，0.7至27）。肺水肿液中前胶原III水平升高所反映的肺中胶原蛋白合成在急性肺损伤的最初24小时内就开始了，同时伴有内皮和上皮对蛋白质通透性增加的急性期。这一证据表明，在临床急性肺损伤过程中，肺纤维化性肺泡炎开始的时间比之前认为的要早得多。此外，前胶原III水平升高是预后不良的早期预测指标。因此，肺水肿液中前胶原III水平升高在急性肺损伤患者中可能具有发病机制和预后两方面的意义。
