Madtes D K, Rubenfeld G, Klima L D, Milberg J A, Steinberg K P, Martin T R, Raghu G, Hudson L D, Clark J G
Sections of Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092, USA.
Am J Respir Crit Care Med. 1998 Aug;158(2):424-30. doi: 10.1164/ajrccm.158.2.9711112.
The acute respiratory distress syndrome (ARDS) frequently results in a fibroproliferative response that precludes effective alveolar repair. Transforming growth factor-alpha (TGF-alpha), a potent epithelial and mesenchymal cell mitogen, may modulate the response to lung injury. In this study, we determined whether bronchoalveolar lavage fluid (BALF) concentrations of TGF-alpha are increased during the first 2 wk after the onset of ARDS and, if so, whether increased TGF-alpha levels in lavage fluid are associated with increased levels of procollagen peptide III (PCP III), a biological marker of fibroproliferation, and with increased fatality rates. We enrolled 74 consecutive patients with ARDS prospectively identified on admission to the intensive care unit of a tertiary care hospital, and 11 patients with chronic interstitial lung disease. Thirteen healthy volunteers served as control subjects. TGF-alpha concentrations were measured in BALF recovered on Days 3, 7, and 14 after the onset of ARDS (total of 130 lavage samples). TGF-alpha was detected in the lavage fluid of 90% of patients with ARDS (67 of 74), and in 100% of patients with idiopathic pulmonary fibrosis (IPF) (10 of 10), but in none of 13 normal volunteers. At each day tested, the median lavage TGF-alpha level of patients with ARDS was significantly higher than that of normals. The overall fatality rate was 45% (33 of 74 patients). In a univariate analysis, the median TGF-alpha levels in nonsurvivors were 1.5-fold higher at Day 7 (p = 0.06) and 1.8-fold higher at Day 14 (p = 0.048). The fatality rate was 4 times higher (CI 1.6, 17.5) for patients with both increased lavage TGF-alpha and PCP III concentrations at Day 7 than for patients with low TGF-alpha and PCP III values, indicating a synergistic relationship between TGF-alpha and PCP III. We conclude that increased levels of TGF-alpha in BALF are common in patients with ARDS and that lavage TGF-alpha is associated with a marker of the fibroproliferative response in sustained ARDS.
急性呼吸窘迫综合征（ARDS）常导致纤维增生反应，阻碍有效的肺泡修复。转化生长因子-α（TGF-α）是一种强大的上皮和间充质细胞有丝分裂原，可能调节对肺损伤的反应。在本研究中，我们确定了ARDS发病后前2周内支气管肺泡灌洗液（BALF）中TGF-α的浓度是否升高，如果升高，灌洗液中TGF-α水平升高是否与前胶原肽III（PCP III）水平升高相关，PCP III是纤维增生的生物标志物，以及是否与死亡率升高相关。我们前瞻性纳入了74例在一家三级医院重症监护病房入院时确诊的ARDS连续患者，以及11例慢性间质性肺疾病患者。13名健康志愿者作为对照。在ARDS发病后第3、7和14天采集的BALF中测量TGF-α浓度（共130份灌洗样本）。90%的ARDS患者（74例中的67例）灌洗液中检测到TGF-α，100%的特发性肺纤维化（IPF）患者（10例中的10例）灌洗液中检测到TGF-α，但13名正常志愿者中均未检测到。在每个检测日，ARDS患者灌洗TGF-α水平中位数显著高于正常对照。总体死亡率为45%（74例患者中的33例）。单因素分析显示，非幸存者第7天TGF-α水平中位数高1.5倍（p = 0.06），第14天高1.8倍（p = 0.048）。第7天灌洗TGF-α和PCP III浓度均升高的患者死亡率比TGF-α和PCP III值低的患者高4倍（CI 1.6，17.5），表明TGF-α与PCP III之间存在协同关系。我们得出结论，ARDS患者BALF中TGF-α水平升高很常见，且灌洗TGF-α与持续性ARDS中纤维增生反应的标志物相关。
