Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome
Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome
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DOI：
10.1016/s1096-7192(02)00044-6
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发表时间：
2002-07-01
影响因子：
3.8
通讯作者：
Gochuico, B
中科院分区：
文献类型：
--
作者：
Gahl, WA;Brantly, M;Gochuico, B
Hermansky-Pudlak综合征（HPS）由皮肤白化病、血小板储存池缺陷和HPS1基因突变患者进行性致死性肺纤维化组成。我们研究了抗纤维化药物吡非尼酮（800mg, t.i.d）治疗21名成年波多黎各HPS1患者的安全性和有效性，其中包括20名HPS1突变纯合子。在一项为期44个月的随机安慰剂对照试验中，每4个月对患者进行一次检查，以肺功能值的变化率作为结果参数。使用130例入院患者的完整数据集，重复测量模型显示，11名吡非尼酮治疗患者的FVC丢失率为每年预测的5%（类似于400 mL），比10名安慰剂治疗患者慢（p = 0.001）。随机系数模型无显著差异。然而，使用的数据仅限于初始FVC为预测值的50%的患者，两种模型都显示吡非尼酮组的FVC （p < 0.022）、FEV(1) （p < 0.0007）、TLC （p < 0.001）和DLCO （p < 0.122）的下降速度与安慰剂组相似，为8%/年。两组的临床和实验室副作用相似。吡非尼酮似乎可以减缓肺功能明显残留的HPS患者肺纤维化的进展。(C) 2002 Elsevier Science （USA）。版权所有。
Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted (similar to400 mL) per year slower than 10 placebo-treated patients (p = 0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC > 50% of predicted, both models showed the pirfenidone group losing FVC (p < 0.022), FEV(1) (p < 0.0007), TLC (p < 0.001), and DLCO (p < 0.122) at a rate similar to8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function. (C) 2002 Elsevier Science (USA). All rights reserved.