Relationship between neutrophil elastase and acute lung injury in humans.
We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. Afterwards, an unblinded study (Study 2) in 20 patients was conducted using procedures for weaning from mechanical ventilation to reevaluate its efficacy with ventilator-free days (VFD) value, the primary endpoint, and to compare with that of Study 1 subgroup, which met the selection criteria used in Study 2. Sivelestat increased PFI rating, reduced duration of mechanical ventilation, and shortened stay in ICU in Study 1, although there was no significant efficacy on the survival rate. VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans.
National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-0042, Japan.
Shouetsu
S
Tamakuma
Michio
M
Ogawa
Naoki
N
Aikawa
Tatsuya
T
Kubota
Hiroyuki
H
Hirasawa
Akitoshi
A
Ishizaka
Nobuyuki
N
Taenaka
Chikuma
C
Hamada
Shozo
S
Matsuoka
Taira
T
Abiru
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D019272:Leukocyte Elastase / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000401:mortality / Q000628:therapy*; D012129:Respiratory Function Tests; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D015300:Ventilator Weaning / Q000379:methods
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine