Marshall R P, Bellingan G, Webb S, Puddicombe A, Goldsack N, McAnulty R J, Laurent G J
Centre for Respiratory Research, Royal Free and University College London Medical School, Rayne Institute, London, United Kingdom.
Am J Respir Crit Care Med. 2000 Nov;162(5):1783-8. doi: 10.1164/ajrccm.162.5.2001061.
The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31-164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11-42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6-14.8 versus 1.1 U/ml; range 0.4-3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0. 6-11.4 versus 0.46 U/ ml; range 0.00-1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45-120 versus 31%; range 16-64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.
急性呼吸窘迫综合征（ARDS）的纤维增殖期传统上被视为晚期事件，但最近的研究表明，在诊断后24小时内肺胶原蛋白更新增加，这对该观点提出了挑战。我们假设纤维增殖在ARDS早期就已开始，其特征是肺中存在成纤维细胞生长因子活性，并且与临床结果相关。符合美国/欧洲共识委员会ARDS标准的患者以及因非ARDS呼吸衰竭接受通气的对照患者在诊断后24小时内进行支气管肺泡灌洗（BAL）和血清采样，并在7天时再次进行。研究了BALF在体外刺激人肺成纤维细胞增殖的能力与BALF/血清中III型前胶原N端肽（N-PCP-III）浓度及临床指标的关系。在24小时时，ARDS灌洗液显示出强大的促有丝分裂活性，中位数相当于对血清反应的70%（范围31-164），且显著高于对照灌洗液（血清反应的32%，范围11-42；p<0.05）。在24小时时，ARDS组血清N-PCP-III浓度高于对照患者（2.8 U/ml；范围0.6-14.8对1.1 U/ml；范围0.4-3.7，p<0.0001），BALF N-PCP-III浓度也是如此（2.9 U/ml；范围0.6-11.4对0.46 U/ml；范围0.00-1.63，p<0.01）。此外，ARDS非幸存者在24小时时的BALF N-PCP-III浓度显著高于幸存者（p<0.05）。在7天时，ARDS组的促有丝分裂活性仍高于对照组（p<0.05），且ARDS非幸存者也显著高于幸存者（67%；范围45-120对31%；范围16-64，p<0.05）。这些数据与纤维增殖是对肺损伤的早期反应且是重要治疗靶点的假设一致。
