Tsangaris Iraklis, Tsantes Argiris, Bonovas Stefanos, Lignos Michalis, Kopterides Petros, Gialeraki Argiro, Rapti Evdoxia, Orfanos Stylianos, Dimopoulou Ioanna, Travlou Anthi, Armaganidis Apostolos
2nd Department of Critical Care Medicine, Attikon Hospital, Medical School, University of Athens, Athens, Greece.
Thromb Res. 2009 Apr;123(6):832-6. doi: 10.1016/j.thromres.2008.07.018. Epub 2008 Sep 20.
Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS.
52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days.
17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively).
ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.
纤溶酶原激活物抑制剂-1（PAI-1）水平升高与急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）的不良预后相关。PAI-1基因启动子区域的单个鸟苷插入/缺失（4G/5G）多态性可能在PAI-1表达的调节中起重要作用。本研究的目的是评估这种多态性对重症ALI/ARDS患者预后的影响。
对52例连续接受机械通气的ALI/ARDS患者进行研究。在诊断后48小时内进行支气管肺泡灌洗。检测血浆和支气管肺泡灌洗液（BALF）中PAI-1活性及D-二聚体水平，并进行PAI-1的4G/5G基因分型。主要结局为28天死亡率，次要结局包括器官功能障碍和无呼吸机天数。
17例患者为4G等位基因纯合子。研究入组时各亚组间严重程度评分无差异。4G-4G患者和非4G-4G患者的28天死亡率分别为70.6%和42.9%（p=0.06）。4G-4G亚组和非4G-4G亚组之间血浆和BALF中的PAI-1活性水平及D-二聚体无显著差异。多因素分析中，4G/4G基因型是唯一与28天死亡率独立相关的变量（比值比=9.95，95%可信区间：1.79-55.28，p=0.009）。此外，4G/4G基因型和血浆PAI-1活性水平与无呼吸机天数独立负相关（分别为p=0.033和p=0.008）。
PAI-1基因4G等位基因纯合的ALI/ARDS患者28天死亡率更高。这种基因型与无辅助通气天数减少相关，且与无器官衰竭天数呈负相关。
