Rabinovitch Nathan, Zhang Lening, Gelfand Erwin W
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2006 Sep;118(3):635-40. doi: 10.1016/j.jaci.2006.05.011. Epub 2006 Jul 27.
Use of leukotriene receptor antagonists improves disease control in children and adults with asthma. However, the relationship between cysteinyl leukotriene levels and indices of daily asthma control has not been studied directly.
We sought to assess the relationship between daily variability in urinary leukotriene E(4) (LTE(4)) levels and daily lung function in children primarily taking inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs).
Fifty children primarily with moderate-to-severe asthma were followed with measurements of urinary LTE(4), monitoring of FEV(1), and albuterol use.
Increasing urinary LTE(4) levels were associated with significant (P = .006) decreases in percent predicted FEV(1) (ppFEV(1)) averaging 4.7% per interquartile range increase in LTE(4) and accompanied by increased albuterol use (P = .03). Children with lower FEV(1)/forced vital capacity ratios demonstrated larger LTE(4)-related FEV(1) decreases (6.4%) compared to those with higher ratios (4.2%, P = .009). This association was blunted in children taking montelukast (1.4% ppFEV(1) decrease) compared with that in children not taking this medication (5.4% ppFEV(1) decrease, P = .05). Children with lower lung function ratios demonstrated greater blunting of the LTE(4) effect with montelukast (0.9% ppFEV(1) decrease) compared to those with higher ratios (3.6% ppFEV(1), P = .0002).
Daily variability in LTE(4) levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE(4) levels, leukotriene receptor antagonists protect against daily FEV(1) decreases. This protection might be greatest in those with persistent airway obstruction despite use of ICS and LABA therapy.
Therapies designed to block cysteinyl leukotriene production or function might benefit children receiving ICS and LABA therapy who continue to experience persistent disease.
白三烯受体拮抗剂的使用可改善哮喘儿童和成人的疾病控制情况。然而，半胱氨酰白三烯水平与每日哮喘控制指标之间的关系尚未得到直接研究。
我们旨在评估主要使用吸入性糖皮质激素（ICS）和长效β受体激动剂（LABA）的儿童尿白三烯E4（LTE4）水平的每日变化与每日肺功能之间的关系。
对50名主要患有中度至重度哮喘的儿童进行随访，测量尿LTE4、监测第一秒用力呼气容积（FEV1）以及沙丁胺醇的使用情况。
尿LTE4水平升高与预计FEV1百分比（ppFEV1）显著下降相关（P = 0.006），LTE4每增加一个四分位数间距，ppFEV1平均下降4.7%，同时沙丁胺醇的使用增加（P = 0.03）。与FEV1/用力肺活量比值较高的儿童相比，FEV1/用力肺活量比值较低的儿童LTE4相关的FEV1下降幅度更大（6.4%）（4.2%，P = 0.009）。与未服用孟鲁司特的儿童相比，服用孟鲁司特的儿童这种关联减弱（ppFEV1下降1.4%）（ppFEV1下降5.4%，P = 0.05）。与FEV1/用力肺活量比值较高的儿童相比，FEV1/用力肺活量比值较低的儿童孟鲁司特对LTE4效应的减弱作用更大（ppFEV1下降0.9%）（ppFEV1下降3.6%，P = 0.0002）。
LTE4水平的每日变化与肺功能的临床显著下降相关。在尿LTE4水平升高相关反应的儿童中，白三烯受体拮抗剂可防止每日FEV1下降。在尽管使用ICS和LABA治疗仍存在持续性气道阻塞的儿童中，这种保护作用可能最大。
旨在阻断半胱氨酰白三烯产生或功能的疗法可能使接受ICS和LABA治疗但仍患有持续性疾病的儿童受益。
