Tolerance and rebound with zafirlukast in patients with persistent asthma.
Tolerance and rebound with zafirlukast in patients with persistent asthma.
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DOI：
10.1186/1477-5751-7-3
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发表时间：
2008-05-19
期刊：
影响因子：
--
通讯作者：
Walters EH
中科院分区：
文献类型：
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作者：
Reid DW;Misso NL;Aggarwal S;Thompson PJ;Johns DP;Walters EH
扎鲁司特（一种半胱氨酰白三烯 (CysLT) 受体拮抗剂 (LRA)）在持续性哮喘中产生耐受性的可能性尚未得到专门研究。寻找 LRA 戒断后耐受性和短期临床恶化可能性的任何证据。结果衡量标准包括以下方面的变化：对吸入乙酰甲胆碱 (PD20FEV1) 的气道高反应性、日常症状和呼气峰流量 (PEF)、痰和血细胞特征、痰 CysLT 和前列腺素 (PG)E2 以及呼出一氧化氮 (eNO) 水平。一项扎鲁司特双盲、安慰剂对照研究，21 名仅服用 β2 激动剂的哮喘患者（第 I 组）和 24 名接受 ICS 治疗的受试者（第 II 组）在 12 周内每天两次服用 20 毫克扎鲁司特。在第一组中，与安慰剂相比，扎鲁司特显着改善了早晨的 PEF 和 FEV1（p < 0.01），并在两周后减少了早晨醒来时患有哮喘的情况（p < 0.05）。同样，在第 II 组中，与安慰剂相比，FEV1 有所改善 (p < 0.05)，并且治疗组内早期 PEF、β2 激动剂使用和哮喘严重程度评分均有所改善 (p < 0.05)。然而，在 12 周内，第一组中扎鲁司特的大部分改善以及第二组中较小程度的改善都向基线值恶化。与安慰剂相比，两组患者在扎鲁司特停药后一周，早上和晚上的 PEF 和 FEV1 均显着恶化 (p ≤ 0.05)，并且第 II 组夜间觉醒次数增加 (p < 0.05)。 PD20FEV1、痰 CysLT 浓度或呼出一氧化氮 (eNO) 水平没有变化。然而，与安慰剂相比，扎鲁司特停药后，两组的血液中性粒细胞均显着增加（p = 0.007）。扎鲁司特似乎出现了耐受性，并且停药后出现反弹性临床恶化，并伴有血液中性粒细胞增多。
The potential for tolerance to develop to zafirlukast, a cysteinyl leukotriene (CysLT) receptor antagonist (LRA) in persistent asthma, has not been specifically examined. To look for any evidence of tolerance and potential for short-term clinical worsening on LRA withdrawal. Outcome measures included changes in; airway hyperresponsiveness to inhaled methacholine (PD20FEV1), daily symptoms and peak expiratory flows (PEF), sputum and blood cell profiles, sputum CysLT and prostaglandin (PG)E2 and exhaled nitric oxide (eNO) levels. A double blind, placebo-controlled study of zafirlukast, 20 mg twice daily over 12 weeks in 21 asthmatics taking β2-agonists only (Group I), and 24 subjects treated with ICS (Group II). In Group I, zafirlukast significantly improved morning PEF and FEV1compared to placebo (p < 0.01), and reduced morning waking with asthma from baseline after two weeks (p < 0.05). Similarly in Group II, FEV1 improved compared to placebo (p < 0.05), and there were early within-treatment group improvements in morning PEF, β2-agonist use and asthma severity scores (p < 0.05). However, most improvements with zafirlukast in Group I and to a lesser extent in Group II deteriorated toward baseline values over 12 weeks. In both groups, one week following zafirlukast withdrawal there were significant deteriorations in morning and evening PEFs and FEV1 compared with placebo (p ≤ 0.05) and increased nocturnal awakenings in Group II (p < 0.05). There were no changes in PD20FEV1, sputum CysLT concentrations or exhaled nitric oxide (eNO) levels. However, blood neutrophils significantly increased in both groups following zafirlukast withdrawal compared to placebo (p = 0.007). Tolerance appears to develop to zafirlukast and there is rebound clinical deterioration on drug withdrawal, accompanied by a blood neutrophilia.