Effect of montelukast on time‐course of exhaled nitric oxide in asthma: Influence of LTC4 synthase A−444C polymorphism
Effect of montelukast on time‐course of exhaled nitric oxide in asthma: Influence of LTC4 synthase A−444C polymorphism
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孟鲁司特对哮喘呼出一氧化氮时程的影响：LTC4合酶A−444C多态性的影响
作者：
G. Whelan;K. Blake;N. Kissoon;L. Duckworth;Jainwei Wang;James E. Sylvester;J. Lima
白三烯(LT)介导哮喘的炎症反应。呼出的一氧化氮(FeNO)被认为是评估哮喘患者呼吸道炎症和药物抗炎作用的一种敏感和可重复性的方法。已知有许多因素导致患者体内FeNO的变化，这可能会混淆解释。本研究的目的是表征FeNO的时程，确定孟鲁司特对FeNO时程的影响，并评价LTC4合成酶A−444c多态性对孟鲁司特引起的FeNO变化的影响。经过两周的磨合，10-16岁的7名男性和5名女性哮喘患者在睡前以双盲交叉方式服用5或10毫克的孟鲁司特或相同的安慰剂，持续7天，然后进行7天的冲洗。在基线和治疗的第1、2、3、7天，每30分钟测定一次FENO，持续3或6小时。计算FeNO的时间平均值(FeNO*)，并比较安慰剂和孟鲁司特治疗后FeNO*相对于基线和时间的百分比变化。用聚合酶链式反应和限制性片段长度多态性方法检测A−444c基因多态性。在每个患者中，FeNO随着时间的变化而显著变化。安慰剂和孟鲁司特治疗期间FeNO(FeNO*)的时间平均值相似。孟鲁司特显著降低杂合子(n = 4)FeNO*-时间曲线的斜率，但对A/A纯合子(n = 8)无明显影响。这些数据表明，与A/A纯合子相比，杂合子对孟鲁司特的反应更好，至少在FeNO变化方面是这样。我们的结论是，基于FeNO的单一测定来评估炎症或药物在哮喘中的抗炎作用可能具有误导性。我们进一步得出结论，LTC4合酶基因的A−444c多态可能是孟鲁司特引起的FeNO*变化的患者间差异的原因，值得进一步研究。儿科肺单醇。2003；36：413-420。©2003 Wiley-Liss公司
Leukotrienes (LT) mediate inflammation in asthma. The fraction of exhaled nitric oxide (FENO) is thought to be a sensitive and reproducible method for assessing airway inflammation in asthmatics and the anti‐inflammatory effects of drugs. A number of factors are known to contribute to intrapatient variation in FENO which can confound interpretation. The aims of this study were to characterize the time‐course of FENO, determine the effect of montelukast on the time‐course of FENO, and evaluate the influence of the LTC4 synthase A−444C polymorphism on montelukast‐evoked changes in FENO. Following a 2‐week run‐in, 7 males and 5 females with asthma, 10–16 years old, received 5 or 10 mg of montelukast or an identical placebo at bedtime for 7 days in double‐blind, crossover fashion, followed by a 7‐day washout. FENOwas quantified every 30 min for 3 or 6 hr at baseline and on days 1, 2, 3, and 7 of treatment. A time‐averaged value for FENO was calculated (FENO*), and % changes in FENO* relative to baseline vs. time following placebo and montelukast were compared. The genotype of the A−444C polymorphism was determined by PCR and RFLP. FENO varied markedly as a function of time in each patient. Time‐averaged values of FENO (FENO*) during placebo and montelukast treatment were similar. Montelukast significantly reduced the slope of the % change in FENO* vs. time curve in heterozygotes (n = 4), but not in A/A homozygotes (n = 8). These data suggest that heterozygotes respond better to montelukast compared to A/A homozygotes, at least with respect to changes in FENO. We conclude that assessment of inflammation or the anti‐inflammatory effects of drugs in asthma based on single determinations of FENO can be misleading. We further conclude that the A−444C polymorphism in the LTC4 synthase gene probably contributes to interpatient variability in montelukast‐evoked changes in FENO* and warrants further study. Pediatr Pulmonol. 2003; 36:413–420. © 2003 Wiley‐Liss, Inc.
糖皮质激素紧急治疗儿童哮喘急性加重期间呼出一氧化氮与肺活量测定的比较。
DOI：
10.1016/s1081-1206(10)62591-4
发表时间：
1999
期刊：
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
影响因子：
--
作者：
Lanz,MJ;Leung,DY;White,CW
通讯作者：
White,CW
哮喘患者呼出一氧化氮：与 NOS1 基因型相关。
DOI：
10.1164/ajrccm.162.6.2003089
发表时间：
2000
期刊：
American journal of respiratory and critical care medicine.
影响因子：
--
作者：
Wechsler,ME;Grasemann,H;Deykin,A;Silverman,EK;Yandava,CN;Israel,E;Wand,M;Drazen,JM
通讯作者：
Drazen,JM
一种在分子流行病学研究中获取基因组 DNA 的简单漱口方法。
DOI：
--
发表时间：
1998
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
影响因子：
--
作者：
Lum,A;LeMarchand,L
通讯作者：
LeMarchand,L