Administration Of Neutrophil Elastase Inhibitor Research Articles

Study on Perioperative Administration of a Neutrophil Elastase Inhibitor for Interstitial Pneumonias

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.

P3.04-029 A Prospective Randomized Trial of Perioperative Administration of Neutrophil Elastase Inhibitor in Patients with Interstitial Pneumonias: Topic: Miscellaneous II

Although the acute exacerbation of interstitial pneumonia is a lethal complication after pulmonary resection for lung cancer patients with idiopathic interstitial pneumonias (IIPs), there are no established methods to prevent its occurrence. This prospective randomized study was conducted to evaluate whether the perioperative administration of neutrophil elastase inhibitor prevents the acute exacerbation of interstitial pneumonia. Between October 2009 and April 2015, 130 IIP patients with suspected lung cancer tumors were randomly assigned to two groups before surgery: in Group A (n=65), sivelestat sodium hydrate was perioperatively administered for 5 days; in Group B (n=65), no medications were administered. The primary endpoint was the frequency of the acute exacerbation of IIPs. The secondary endpoints were perioperative changes in the patients’ LDH, CRP, KL-6, SP-D and SP-A values, and the safety of the preoperative administration of sivelestat sodium hydrate. Multivariate analyses were performed using a logistic regression model to identify the predictors of acute exacerbation. IIPs was radiologically classified into the following patterns: usual interstitial pneumonia (UIP) (n=23), possible UIP (n=28) and inconsistent with UIP (n=23). Sublobar resection, lobectomy and pneumonectomy were performed in 16, 112, and 2 patients, respectively. There were no statistically significant differences in patient characteristics between the groups. Two patients in group A and one patient in group B developed an acute exacerbation of IIPs. A preoperative partial pressure oxygen (PaO2) level of < 70mmHg was the only predictive factor identified in the multivariate analysis (p = 0.019, HR 19.2). The administration of neutrophil elastase was not associated with the development of an acute exacerbation, or with short- or long-term mortality. The KL-6, SP-D, SP-A levels on postoperative days 1 and 5 were lower in group A than in group B, and the LDH and CRP levels on postoperative day 5 were lower in group B than in group A; however the differences were not statistically significant. No subjective adverse events that could potentially be attributed to the administration of neutrophil elastase inhibitor were observed. The perioperative administration of neutrophil elastase inhibitor appeared to be safe; however, it could not prevent the development of acute exacerbation after pulmonary resection in lung cancer patients with IIPs.

Optimal Period for the Prophylactic Administration of Neutrophil Elastase Inhibitor for Patients with Esophageal Cancer Undergoing Esophagectomy

The present study was designed to determine the optimal period for the prophylactic administration of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing transthoracic esophagectomy. Sivelestat is reported to be effective in patients who undergo esophagectomy by providing an increased oxygenation ability and suppressing the serum inflammatory cytokines in the postoperative period. However, the optimal period for the prophylactic administration of Sivelestat remains to be elucidated. The 30 patients who underwent esophagectomy for thoracic esophageal cancer were enrolled in one of two groups. The initial 15 patients were assigned to group A and received intravenous infusion of Sivelestat sodium hydrate until postoperative day (POD) 2, and the subsequent 15 patients were assigned to group B and received Sivelestat until POD 5. Historical controls without Sivelestat administration were used. The postoperative courses and serum inflammatory cytokines were evaluated. Sivelestat improved oxygenation in the postoperative period; however, there were no differences between the two groups in terms of duration of mechanical ventilation, intensive care unit stay, systemic inflammatory response syndrome, and postoperative change of oxygenation. In addition, there were no differences in the postoperative changes in the serum interleukin (IL)-6 and high mobility group box chromosomal protein 1. Although the serum IL-8 on POD 3 was lower in group B than in group A, the neutrophil elastase showed no difference between these groups. None of the patients in either group suffered respiratory complications. The two-day administration of Sivelestat initiated immediately after intrathoracic manipulation was found to be sufficient for prophylactic use to prevent pulmonary complications by suppressing hypercytokinemia after esophagectomy.

The effects of sivelestat sodium hydrate on uterine contraction and the concentration of maternal and fetal blood cytokines in a sheep model of intra-amniotic infection induced by lipopolysaccharide

Objective. To evaluate the effects of a neutrophil elastase inhibitor, sivelestat sodium hydrate, in a sheep model of intra-amniotic infection(IAI) induced by lipopolysaccharide (LPS) injected into the intra-amniotic compartment.Methods. We examined 15 chronically instrumented ewes, the ewes were assigned randomly as group A (five ewes) administered an antibiotic after LPS administration, group B (five ewes) administered a neutrophil elastase inhibitor (0.2 mg/kg/h) with an antibiotic after LPS administration, and group C (five ewes) a sham operation group. Uterine contraction was evaluated by fetal tracheal pressure and concentrations of PGE2, IL-6, IL-8, TNF-α in maternal and fetal blood before and after LPS administration were measured chronologically.Results. (1) All ewes of group A delivered within 72 h, but only one ewe of group B delivered. Uterine contraction of group B was suppressed about 60% in comparison with group A. (2) Maternal blood concentrations of PGE2, IL-6, IL-8, and TNF-α level of group A increased chronologically and when compared with groups B and C the increase was significantly higher. (3) There were no significant changes in the fetal blood cytokines in any of the three groups.Conclusion. Administration of neutrophil elastase inhibitor might suggest a useful strategy to prevent premature delivery resulting from intrauterine infection.