The efficacy and safety of KL(4)-surfactant in infants with respiratory distress syndrome
The efficacy and safety of KL(4)-surfactant in infants with respiratory distress syndrome
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DOI：
10.1164/ajrccm.153.1.8542150
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发表时间：
1996-01-01
影响因子：
24.7
通讯作者：
Alberts, MS
中科院分区：
文献类型：
--
作者：
Cochrane, CG;Revak, SD;Alberts, MS
本研究旨在确定一种合成肽 KLLLLKLLLLKLLLLKLLLLK (KL(4))（其中 K = 赖氨酸和 L = 亮氨酸）在磷脂水分散体（DPPC 和 POPG）中是否会扩张患有呼吸窘迫综合征 (RDS) 的早产儿的肺泡并改善气体交换。 KL(4) 肽的合成类似于表面活性剂蛋白 B (SP-B) 的氨基酸模式。 47 名患有 RDS 的婴儿在出生后 4 小时内接受了 KL(4)-肽/磷脂混合物（称为 KL(4)-表面活性剂）的治疗。疗效分析中纳入的 39 名患者的平均动脉与肺泡氧张力比 (a/A O-2) 在 12 小时龄时从治疗前值 0.14 +/- 0.02（平均值 +/- SEM）上升至 0.40 +/- 0.04（正常值大于或等于 0.40）。平均气道压力和氧合指数值同时下降，并且在X光片上观察到肺部扩张。机械通气的中位持续时间为 5.0 d。在 39 名婴儿中，29 名只需要单剂。放射线数据表明，那些需要第二次滴注 KL(4)-表面活性剂但 a/A O-2 比率未显示持续上升的患者实际上确实表现出肺泡扩张。没有发生与 RDS 相关的死亡；并发症的发生率并不高于其他已发表的可比研究中发现的情况。数据表明，模拟 SP-B 疏水性和亲水性模式的合成肽 KL(4)，当与磷脂 DPPC 和 POPG 配制在水分散体中时，可产生强大且持久的表面活性剂活性，这一点通过 RDS 婴儿的肺泡扩张和气体交换改善来判断。
The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL(4)), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL(4) peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL(4)-peptide/phospholipid mixture, called KL(4)-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O-2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value greater than or equal to 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL(4)-Surfactant but not showing a sustained rise in a/A O-2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL(4), which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.