Fukui Mariko, Takamochi Kazuya, Oh Shiaki, Matsunaga Takeshi, Suzuki Kazuhiro, Ando Katsutoshi, Suzuki Kenji
Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
Ann Thorac Surg. 2017 Jun;103(6):1781-1787. doi: 10.1016/j.athoracsur.2016.12.022. Epub 2017 Mar 27.
Although acute exacerbation of idiopathic interstitial pneumonias (IIPs) is a lethal complication after pulmonary resection for lung cancer with IIPs, there are no established methods to prevent its occurrence. This prospective randomized study was conducted to evaluate whether perioperative administration of the neutrophil elastase inhibitor sivelestat prevents acute exacerbation after surgery.
The IIP patients with suspected lung cancers were randomly assigned to two groups before surgery: in group A (n = 65), sivelestat was perioperatively administered for 5 days; in group B (n = 65), no medications were administered. The primary endpoint was the frequency of acute exacerbation of IIPs. The secondary endpoints were perioperative changes in the lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, surfactant protein D and surfactant protein A values, and the safety of preoperative administration of sivelestat. Multivariate analyses were performed using a logistic regression model to identify the factors that predicted acute exacerbation.
Acute exacerbation developed in 2 patients in group A and 1 patient in group B (p = 0.559). Administration of sivelestat did not contribute to decreasing the acute exacerbation as well as short- and long-term mortality. The differences were not statistically significant in perioperative lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, and surfactant protein D and A levels. No subjective adverse events were observed. A preoperative partial pressure oxygen level of less than 70 mm Hg was the only predictive factor identified in the logistic analysis (p = 0.019, hazard ratio 19.2).
Perioperative administration of neutrophil elastase inhibitor appeared to be safe; however, it could not prevent the development of acute exacerbation after surgery in lung cancer patients with IIPs.
尽管特发性间质性肺炎（IIP）急性加重是肺癌合并IIP患者肺切除术后的致命并发症，但尚无预防其发生的既定方法。本前瞻性随机研究旨在评估围手术期给予中性粒细胞弹性蛋白酶抑制剂西维来司他是否能预防术后急性加重。
疑似肺癌的IIP患者在手术前随机分为两组：A组（n = 65），围手术期给予西维来司他5天；B组（n = 65），不给予任何药物。主要终点是IIP急性加重的发生率。次要终点是围手术期乳酸脱氢酶、C反应蛋白、唾液酸化碳水化合物抗原、表面活性蛋白D和表面活性蛋白A值的变化，以及术前给予西维来司他的安全性。使用逻辑回归模型进行多变量分析，以确定预测急性加重的因素。
A组有2例患者发生急性加重，B组有1例患者发生急性加重（p = 0.559）。给予西维来司他对降低急性加重以及短期和长期死亡率并无作用。围手术期乳酸脱氢酶、C反应蛋白、唾液酸化碳水化合物抗原以及表面活性蛋白D和A水平的差异无统计学意义。未观察到主观不良事件。逻辑分析中确定的唯一预测因素是术前氧分压低于70 mmHg（p = 0.019，风险比19.2）。
围手术期给予中性粒细胞弹性蛋白酶抑制剂似乎是安全的；然而，它不能预防IIP肺癌患者术后急性加重的发生。
