Cantin André M, Berthiaume Yves, Cloutier Diane, Martel Marc
Respiratory Division, Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Quebec.
Clin Invest Med. 2006 Aug;29(4):201-7.
Neutrophil elastase in the cystic fibrosis airways inhibits opsonophagocytosis and induces the expression of interleukin-8, a neutrophil chemoattractant. Prolastin is a therapeutic preparation of alpha-1 proteinase inhibitor (alpha1,-PI), a neutrophil elastase inhibitor. The objective of this study was to determine the effects of Prolastin aerosol therapy on airway inflammation in cystic fibrosis.
The primary endpoint of this study was sputum taurine, an amino-acid present in high concentrations in neutrophils. Sputum taurine correlates with respiratory exacerbations of cystic fibrosis. Seventeen patients with cystic fibrosis were each assigned to three sequential 10-day periods including first, aerosol therapy of 5 ml saline solution bid; second, aerosol therapy of 250 mg Prolastin bid; third, no aerosol therapy. On days 8, 9 and 10 of each period, early morning sputum was collected for the quantification of alpha1-PI, neutrophil elastase activity, IL-8 and taurine.
During Prolastin therapy, a 3-fold increase in sputum alpha1-PI was observed (P = 0.002). Baseline values of sputum alpha1-PI correlated with the values obtained after Prolastin aerosol (R = 0.77, P < 0.01). Sputum neutrophil elastase activity remained unchanged but taurine decreased after Prolastin therapy (during therapy P = 0.052, after therapy P = 0.026). Prolastin aerosol therapy had no adverse effect on pulmonary function.
Aerosol therapy with Prolastin in patients with cystic fibrosis leads to a progressive decrease in sputum taurine. This suggests that even in the absence of sustained elastase inhibition, Prolastin aerosol therapy may have a beneficial effect on airway inflammation in patients with cystic fibrosis.
囊性纤维化气道中的中性粒细胞弹性蛋白酶可抑制调理吞噬作用，并诱导中性粒细胞趋化因子白细胞介素-8的表达。普洛莱斯坦是一种α1-蛋白酶抑制剂（α1-PI）的治疗制剂，α1-PI是一种中性粒细胞弹性蛋白酶抑制剂。本研究的目的是确定普洛莱斯坦雾化吸入疗法对囊性纤维化气道炎症的影响。
本研究的主要终点是痰液中的牛磺酸，牛磺酸是一种在中性粒细胞中高浓度存在的氨基酸。痰液中的牛磺酸与囊性纤维化的呼吸道病情加重相关。17例囊性纤维化患者每人依次接受三个为期10天的阶段治疗，第一阶段，每日两次雾化吸入5毫升盐溶液；第二阶段，每日两次雾化吸入250毫克普洛莱斯坦；第三阶段，不进行雾化吸入治疗（空白对照）。在每个阶段的第8、9和10天，收集清晨痰液，用于定量检测α1-PI、中性粒细胞弹性蛋白酶活性、白细胞介素-8和牛磺酸。
在普洛莱斯坦治疗期间，痰液中的α1-PI增加了3倍（P = 0.002）。痰液α1-PI的基线值与普洛莱斯坦雾化吸入后测得的值相关（R = 0.77，P < 0.01）。痰液中性粒细胞弹性蛋白酶活性保持不变，但普洛莱斯坦治疗后牛磺酸减少（治疗期间P = 0.052，治疗后P = 0.026）。普洛莱斯坦雾化吸入疗法对肺功能无不良影响。
对囊性纤维化患者进行普洛莱斯坦雾化吸入治疗可使痰液中的牛磺酸逐渐减少。这表明，即使没有持续的弹性蛋白酶抑制作用，普洛莱斯坦雾化吸入疗法可能对囊性纤维化患者的气道炎症具有有益作用。
