scholarly journals Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of acute respiratory distress syndrome

Author(s):  
Yasushi Kawasaki ◽  
Naoki Aikawa
Respiration ◽  
2021 ◽  
pp. 1-11
Author(s):  
Hiroyuki Hashimoto ◽  
Shota Yamamoto ◽  
Hiroaki Nakagawa ◽  
Yoshihiro Suido ◽  
Shintaro Sato ◽  
...  

<b><i>Background:</i></b> Surgical lung biopsy (SLB) is performed in patients with acute respiratory distress syndrome (ARDS); however, its clinical utility remains unclear. <b><i>Objectives:</i></b> We categorized the pathological diagnoses and investigated the predictive value for short-term mortality. <b><i>Method:</i></b> Three electronic databases (MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) were searched for the included studies. The QUADAS-2 was used to evaluate the risk of bias and its applicability. The types and populations of pathological diagnoses were investigated. The pooled sensitivity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR) were estimated at a fixed specificity. Hierarchical summary receiver operating characteristic curves were drawn. <b><i>Results:</i></b> A total of 16 studies that enrolled 758 patients were included. The pathological diagnoses were as follows: diffuse alveolar damage (DAD) 29.9%; infection 24.7%; interstitial lung disease 17.2%; malignancy 3.6%; cardiovascular disease 3.6%; drug toxicity 2.3%; connective tissue disease 2.2%; allergic disease 1.1%; and nonspecific diagnosis 15.4%. To predict short-term mortality, 13 studies that enrolled 613 patients used DAD as an index test and recorded a mortality rate of 56.9% (349 of 613 patients). A total of 3 studies that used index tests other than DAD were excluded. The pooled sensitivity, fixed specificity, LR+, LR−, and DOR were 0.46 (95% confidence interval [CI]: 0.29–0.56), 0.69, 1.48 (95% CI: 0.92–1.81), 0.78 (95% CI: 0.63–1.03), and 1.90 (95% CI: 0.89–2.86), respectively. <b><i>Conclusions:</i></b> SLB is unlikely to provide a specific diagnosis and should not be recommended for confirming DAD or predicting ARDS prognosis.


Shock ◽  
2017 ◽  
Vol 48 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Tiehua Wang ◽  
Zhaozhong Zhu ◽  
Zhuang Liu ◽  
Liang Yi ◽  
Zhixu Yang ◽  
...  

1998 ◽  
Vol 275 (2) ◽  
pp. H385-H392 ◽  
Author(s):  
D. Carden ◽  
F. Xiao ◽  
Candace Moak ◽  
Bradley H. Willis ◽  
Sherry Robinson-Jackson ◽  
...  

Intestinal ischemia-reperfusion (I-R) is associated with lung injury and the acute respiratory distress syndrome. The hypothesis of this study was that intestinal I-R activates circulating neutrophils to promote elastase-mediated lung injury. Isolated rat lungs were perfused with blood or plasma obtained after intestinal I-R, and lung neutrophil retention and injury and bronchoalveolar lavage (BAL) elastase were measured. Perfusion with I-R blood caused lung neutrophil accumulation and injury and increased BAL elastase. These effects were attenuated by the elastase inhibitor L-658758. Interference with neutrophil adherence before gut reperfusion blocked BAL elastase accumulation. The role of endothelial junction proteins (cadherins) in I-R-elicited lung damage was also evaluated. Activated human neutrophils proteolyzed cadherins in human umbilical vein endothelial cells. Furthermore, plasma of patients with acute respiratory distress syndrome contained soluble cadherin fragments. The results of this study suggest that the elastase released by systemically activated neutrophils contributes to lung neutrophil accumulation and pulmonary microvascular injury. Elastase-mediated proteolysis of endothelial cell cadherins may represent the mechanism through which lung microvascular integrity is disrupted after intestinal I-R.


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