摘要信息：摘 要 中性粒细胞弹性蛋白酶(NE)是由多形核中性粒细胞释放的弹性蛋白酶,在肺部炎症性疾病发病机制中,既有有利作用,又有不利作用,与体内 NE-抗 NE平衡有关。本文又综述了通过维持 NE-抗 NE平衡来治疗几种炎症性疾病的研究进展及目前存在的问题。

摘要信息：Background:There are conflicting views on the of sivelestat sodium (sivelestat-Na) on acute lung injury. Methods:The efficacy of sivelestat-Na on aspiration-related acute lung injury was analyzed by reviewing case reports published before or after the appearance of the drug on the clinical practice in Japan. Data were analyzed from the 23 sivelestat-treated cases and 5 non-sivelestat cases. Results:Sivelestat-Na was administered by 0.2 mg x kg(-1) x hr(-1) for 10 +/- 4 (mean +/- SD) days. PaO2/ ratio increased significantly from 124 +/- 59 mmHg of baseline to 253 +/- 79 mmHg on the third and to 361 +/- 84 mmHg on the termination of the therapy. Significantly better response was observed if the drug was administered within 24 hours after aspiration for patients with background of neurological disease, in which the increases in the P/F ratio were greater and the duration of the drug administration was shorter compared with other patients. In comparison with the non-sivelestat cases, sivelestat-Na therapy appears to be associated with shorter ventilator days or higher P/F increase, although sivelestat-Na costs higher. Conclusions:These results suggest the possibility of conducting prospective clinical trials to assess the efficacy of early sivelestat-Na therapy for aspiration-related acute lung injury.

摘要信息：The patient was a 67-year-old man with diabetes mellitus who had been to a hot spring spa a few days before his admission. The diagnosis of Legionella pneumonia was made using a urinary antigen assay. Intravenous pazufloxacin and oral clarithromycin were started. However, despite these treatments, he developed acute respiratory distress syndrome (ARDS). He was administered the combination of intravenous pazufloxacin and erythromycin, corticosteroid, and sivelestat for two weeks. Then he was successfully recovered. The outcome suggests that treatment with corticosteroid and sivelestat, in addition to a combination of appropriate anti-Legionella antibiotics, should be considered for patients with severe Legionella pneumonia with ARDS.

摘要信息：It is important to regulate excessive inflammation when patients with severe infectious disease are treated. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used in the treatment of lung injury but its effect on bacterial pneumonia is unknown. The authors examined the efficacy of sivelestat in combination with a fluoroquinolone in a Legionella pneumophila pneumonia mouse model. The combination therapy did not show a significant survival improvement compared to the treatment with fluoroquinolone alone, but reduced bacteria number and inflammatory cells in the early phase. The combination therapy can contribute to treatment of L. pneumophila pneumonia with protecting lungs.

摘要信息：In 2011, during the Great East Japan Earthquake and tsunami, 90% of victims died from drowning. We report on two tsunami survivors with severe pneumonia potentially caused by Legionella pneumophila. Both victims aspirated a large quantity of contaminated water; sand, mud and a variety of microbes were thought to have entered into their lower respiratory tracts. One patient had a mycotic intracranial aneurysm; the other patient had co-infections with several organisms, including Scedosporium species. Although scedosporiosis is a relatively rare infectious disease, symptoms are progressive and prognosis is poor. These pathogens are not specific for tsunami lung, but are reported causative agents for pneumonia after near-drowning.

摘要信息：Background and purpose: Acute exacerbation of interstitial pneumonia is a life-threatening complication after lung cancer surgery. Dorsal subpleural fibrotic changes occupying 3 or more segments of both lower lobes on high-resolution computed tomography indicate a very high risk. We conducted a prospective phase II study to assess the efficacy of prophylactic treatment. Methods: Patients with lung cancer underwent high-resolution computed tomography preoperatively to assess the risk of acute exacerbations of interstitial pneumonia. Before induction of general anesthesia, high-risk patients received 125 mg of methylprednisolone as an intravenous bolus and sivelestat sodium hydrate 300 mg ·day(-1) as a continuous intravenous infusion. From January 2010 through August 2011, a total of 327 patients underwent surgery for lung cancer, and 31 (9.5%) were enrolled. Results: There was no case of acute exacerbation. No adverse events were associated with prophylaxis. Usual interstitial pneumonia was confirmed histopathologically in 25 (80.6%) patients. Four (12.9%) patients had major complications. Usual interstitial pneumonia was diagnosed postoperatively in 4 (1.4%) of 327 patients who did not meet the inclusion criteria, and 1 of these patients died due to acute exacerbation of occult interstitial pneumonia. Conclusion: Perioperative use of sivelestat sodium hydrate and low-dose methylprednisolone may be useful as prophylaxis for acute exacerbation of interstitial pneumonia.

摘要信息：Background and objective: The efficacy of sivelestat, a neutrophil elastase inhibitor, for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains controversial. We investigated the role of sivelestat in ALI/ARDS patients on mortality as an end point between the sivelestat group and the non-sivelestat group within 7 days of admission. Methods: This study was performed using the Japanese nationwide administrative database (Diagnostic Procedure Combination; DPC) in 2012. We employed the propensity score weighting method with a Cox proportional hazards model to compare the mortality between the sivelestat group and the non-sivelestat group. Results: A total of 4276 patients were eligible for this study; 1997 patients were treated with sivelestat and 2279 patients did not receive sivelestat within 7 days of admission. After adjusting for confounds, the mortality within 3 months was significantly lower in the sivelestat group compared with the non-sivelestat group (weighted hazard ratio: 0.83; 95% CI: 0.75-0.93; P < 0.002). Multiple regression analysis revealed that younger age, absence of cancer, no need for haemodialysis and no use of high-dose methylprednisolone were significantly correlated with treatment success (survive). Conclusion: These results of this retrospective and observational study suggest that administration of sivelestat within 7 days of admission may improve the prognosis of patients with ALI/ARDS. To our knowledge, this is the largest study to evaluate the efficacy of sivelestat on ALI/ARDS.

摘要信息：Excessive activation of neutrophils results in the release of neutrophil elastase (NE), which leads to lung injury in severe pneumonia. Previously, we demonstrated a novel immune subversion mechanism involving microbial exploitation of this NE ability, which eventually promotes disruption of the pulmonary epithelial barrier. In the present study, we investigated the effect of NE on host innate immune response. THP-1-derived macrophages were stimulated with heat-killed Streptococcus pneumoniae or lipopolysaccharide in the presence or absence of NE followed by analysis of toll-like receptor (TLR) and cytokine expression. Additionally, the biological significance of NE was confirmed in an in vivo mouse intratracheal infection model. NE downregulated the gene transcription of multiple cytokines in THP-1-derived macrophages through the cleavage of TLRs and myeloid differentiation factor 2. Additionally, NE cleaved inflammatory cytokines and chemokines. In a mouse model of intratracheal pneumococcal challenge, administration of an NE inhibitor significantly increased proinflammatory cytokine levels in bronchoalveolar lavage fluid, enhanced bacterial clearance, and improved survival rates. Our work indicates that NE subverts the innate immune response and that inhibition of this enzyme may constitute a novel therapeutic option for the treatment of pneumococcal pneumonia.

摘要信息：Introduction:Acute exacerbation of interstitial pneumonia (AE-IP) is a lethal complication after lung surgery. We conducted a prospective, multi-institutional phase II trial to assess the efficacy and safety of prophylactic measures. Method:Patients with lung cancer with dorsal subpleural fibrotic changes occupying three or more segments of both lower lobes and planned anatomical lung resection were enrolled. Prior to surgery, patients received a 125-mg bolus injection of methylprednisolone and continuous intravenous infusion of sivelestat sodium hydrate (sivelestat) for 2 days. Results:Sixty-nine patients were analysed. Preoperative high-resolution computed tomography (HRCT) showed 37 (53.6%) cases presented with usual interstitial pneumonia (UIP) and possible UIP pattern. There were 60 lobectomies and 9 segmentectomies. Thirty-eight cases were in clinical stage I. No adverse events associated with prophylaxis were observed. There were four cases of AE-IP (5.8%), higher than the expected 2.0%. Three of the four cases showed inconsistencies with the UIP pattern in preoperative HRCT and were pathologically diagnosed as UIP. All patients died of respiratory failure. Overall, 89.9% were diagnosed as idiopathic interstitial pneumonias; UIP was found in 48 patients (69.6%). Severe post-operative complications occurred in 11.6% of the cases. There were 35 deaths, 17 cases of lung cancer and 11 cases related to interstitial pneumonias. The overall survival rate at 3 years was 41.8% of the total and 47.2% of cases with clinical stage I. Conclusions:Perioperative use of sivelestat and low-dose methylprednisolone in patients with anatomical lung resection was safe but did not prove to be a prophylactic effect for AE-IP.

摘要信息：Purpose: This study aimed to evaluate the efficacy of sivelestat sodium on mortality, oxygenation index, and serum markers in patients with acute respiratory distress syndrome (ARDS) associated with Coronavirus Disease 2019 (COVID-19). Methods: A retrospective analysis was conducted on adult inpatients admitted to the Intensive Care Unit (ICU). The study compared clinical characteristics, laboratory indices, and mortality rates between patients treated with and without sivelestat sodium. Cox regression analysis was employed to assess the effect of sivelestat sodium on the risk of death, oxygenation index, and improvement of serum markers in patients with COVID-19-associated ARDS. Results: A total of 110 patients with COVID-19-associated ARDS were included, with 45 patients in the sivelestat group and 65 patients in the control group. The overall patient mortality rate was 69.1%, with 62.2% in the sivelestat group and 73.8% in the control group. After five days of treatment, the median change from baseline in the oxygenation index was 21 mmHg in the medicated group and -31 mmHg in the control group (p < 0.05). Analysis of the oxygenation index as a clinical endpoint event showed a significantly higher rate of improvement in the sivelestat group compared to the control group (57.8% vs. 38.5%, p < 0.05), and the odds of raising the oxygenation index after treatment were 2.05 times higher in the sivelestat group than in the control group (HR = 2.05, 95%CI: 1.02-4.15, p < 0.05). Among patients with a baseline oxygenation index < 200 mmHg, patients in the sivelestat group had an 86% lower risk of death compared to the control group (HR = 0.14, 95%CI: 0.02-0.81, p < 0.05). Conclusions: Sivelestat sodium demonstrated a significant improvement in the oxygenation index of patients with COVID-19-associated ARDS and was found to considerably reduce the risk of death in patients with a baseline oxygenation index of <200 mmHg.